- Email: [email protected]
Cortical contribution to subthalamic activity during chronic electrical stimulation
300
Abstracts
TMS Poster Only 191
Evoked motor response following deep transcranial magnetic stimulation in a cynomolgus monkey
Ishii K1, Matsuzaka Y2, Izumi S1, Abe T3, Nakazato N4, Okita T5, Yashima Y3, Takagi T5, Nagatomi R1, 1Tohoku university Graduate School of Biomedical Engineering (Sendai, JP); 2 Dept. of Physiol., Graduate Scool of Medical Sciences, Tohoku University (Sendai, JP); 3IFG Co., Ltd. (Sendai, JP); 4Kohnan Hospital (Sendai, JP); 5Institute of Fluid Science, Tohoku University (Sendai, JP) Objective: Transcranial magnetic stimulation (TMS) is a noninvasive technique in which magnetic pulses of the current loops are applied to the brain cortex. It is difficult to stimulate deeper regions of the brain with current TMS techniques, since the magnetic field strength decays in inverse proportion to the square of the distance from the current sources. We have recently developed a new TMS coil to overcome this limitation. The purpose of this study is, therefore, to show the new TMS coil is capable of stimulating deeper regions of the brain by monitoring the evoked motor responses and the silent periods following magnetic pulses delivered to the brain of a cynomolgus monkey. Method: A 5-year-old male cynomolgus monkey weighing 3.8kg was fixed on a primate chair, anesthetized with ketamine. Magnetic stimulus was delivered using a circular coil of 10 turns with internal diameters of 110 mm. The coil was set so that the head was inserted into the coil. The surface of the coil was set either at 0, 10, 20 or 30 mm below a plane including bilateral porus acusticus externus and supraorbital tori. A single electric pulse was applied to the coil at voltages ranging from 500 to 1000 V. The distribution of the pulsed magnetic flux density generated by the coil was numerically calculated with the use of RC integration circuit. Motor evoked potentials were recorded from the right triceps brachii muscle via intramuscular electrodes. The experiment was recorded with a video camera. Result: Fig.1 shows the distribution of the pulsed magnetic flux density generated by the coil. Fig.2. shows a representative electromyogram recording from the triceps brachii muscle, in which a silent period and a secondary response induced by the magnetic stimuli were recorded. Not only upper limb but also lower limb and trunk muscle contractions were elicited by the magnetic pulse. No acute adverse events such as hypotensive shock, epileptic seizure, visual and auditory impairment, and abnormal behaviors were observed. Conclusion: Using a newly designed TMS coil, we could successfully deliver magnetic stimuli to the brain of a cynomolgus monkey that evoked motor responses and silent periods. The fact that our TMS coil did not only elicit contraction of arm muscles, but also of lower limb muscles and trunk muscles, suggests that the new TMS technique is capable of efficiently stimulating deeper regions of the brain for the 1st time in the world.
Movement Disorders Poster Only 192
Cortical contribution to subthalamic activity during chronic electrical stimulation
Modolo J, Beuter A, IMS, UMR CNRS 5218 (Talence, FR) Objective: In Parkinson’s disease (PD), the motor cortex appears to play an important role in the generation of abnormal activity in the motor loop network involving basal ganglia, thalamus and cortex. When activity in this network is disrupted, motor symptoms appear but are alleviated by deep brain stimulation (DBS). We use a computational model to examine cortical contribution during DBS. Exploring brain mechanims underlying the effect of DBS may help us propose less invasive but efficient (cortical) stimulation protocols. Method: We used a multi-scale, population based, mathematical model of the subthalamic nucleus (STN) -the main excitatory structure of the basal ganglia- and the external globus pallidus, which receive cortical and striatal input. The model simulates healthy (stable, low-amplitude) and pathological (5 Hz oscillatory synchronized) activity within these two nuclei. In the pathological state, constant or oscillatory (low-frequency) cortical inputs to the STN are simulated and the ability of DBS to suppress abnormal oscillations (bursts) is explored. Results: In the presence of 10 Hz cortical inputs to the STN, DBS does not suppress abnormal bursts present in the STN and correlated with tremor generation (Figure 1). On the contrary DBS suppresses abnormal bursts when cortical input is constant (not shown).
Conclusion: Results support the view that a functional decoupling takes place between resonant cortical input and STN during DBS in PD. Indeed cortical input to the STN has a frequency similar to that of the STN, enhancing STN abnormal oscillatory behavior. This decoupling may originate from the descending cortical spikes colliding with the antidromic depolarization rising from the STN and induced by DBS. This mechanism could be responsible for clinical improvements. In principle such a
Abstracts functional decoupling may be achieved through cortical stimulation. This could be done in practice by switching from low- to high-pass the filter properties of cortical synapses, thus removing the low-frequency cortical contribution.
tDCS Poster Only 193
Improved deceptive skills by modulating activity in the prefrontal cortex
Fecteau S1, Boggio PS2, Ferreira M2, Pascual-Leone A1, Theoret H3, Fregni F1, Theoret H3, 1BIDMC, Harvard Medical School (, US); 2 Universidade Presbiteriana Mackenzie (Sao Paulo, BR); 3Universite de Montreal (Montreal, CA) From an evolutionary view, deception is among survival behaviors. In human, deceptive ability is crucial to survive and succeed in social situations. This ability appears early in human ontogenesis and follows the developmental course of intricate social communication behaviors. Management of deceptive signals requires knowledge of complex communication rules, such as understanding subtle modulation of facial expressions, vocal information at both linguistic and paralinguistic levels, and reflects efficiency of higher cognitive functions such as theory of mind. Without accurate deceptive ability, one is at risk of being socially vulnerable. For instance, individuals with autism who display social and communication difficulties often fail at understanding deception [1]. In regards to neurobiological foundation, deceptive behaviors elicit a complex neural network and are consistently associated with the prefrontal cortex with a right hemisphere dominance [1]. Activity in the right dorsolateral (DLPFC) and ventrolateral prefrontal cortex is enhanced when contrasting deceptive with truthful verbal or motor responses. Importantly, these activations have been correlated with response time; lengthened response time for deceptive answers is a robust effect [1]. Objective: This work aims at improving deceptive ability in healthy volunteers. Based on findings showing that deception elicits increased activity in the right DLPFC and longer response time, we hypothesized that enhancing activity in the right DLPFC will result in improved deceptive skills, that is decreased response time to produce untruthful answers. Method: We conducted a series of experiment using transcranial direct current stimulation to test this hypothesis. We applied concurrent anodal stimulation to the right DLPFC, known to enhance activity, with cathodal stimulation to the left DLPCF, which downregulates activity, to improve various spontaneous deceptive skills. Results: Volunteers displayed improved deceptive skills after receiving anodal stimulation to the right DLPFC coupled with cathodal to the left DLPFC. They were faster and more accurate than those who received the opposite active stimulation (anodal to the left DLPFC coupled with cathodal to the right DLPFC) and sham stimulation. Conclusion: The present results support the involvement of the DLPFC in deceptive behaviors and contribute to the understanding of social communication behaviors. 1.Spence SA et al. Phil Trans R Soc Lond B 2004
rTMS Poster Only 194
Metaplasticity of cTBS-induced enhancement of corticospinal excitability: Dependence on activation of L-Type voltage-gated Ca21 channels
Wankerl K, Gentner R, Weise D, Zeller D, Classen J, Universita¨t Wu¨rzburg (Wu¨rzburg, DE) Objective: Magnetic theta-burst stimulation (cTBS), a novel non-invasive repetitive magnetic stimulation protocol, modulates human corticospinal
301 excitability bidirectionally in dependence on prior motor activity, consistent with the notion of metaplasticity. However, the physiological foundations of this form of metaplasticity are unclear. Studies in slice preparations have identified Ca21 signalling as a possible underlying mechanism. Here we studied these effects with cTBS in combination with pharmacological interventions in vivo. Methods: In 10 subjects and different sessions, cTBS (50 Hz-bursts of three subtreshold magnetic stimuli repeated at 5 Hz) was applied for a duration of 20 sec after different combinations of premedication with nimodipine, an Ltype voltage gated Ca21 channel antagonist, and prior isometric motor activity of 0 min, 1.5 min and 5 min. Motor evoked potentials (MEPs) from the abductor pollicis brevis muscle were recorded before and within 30 min after intervention as an index of corticospinal excitability. Results: cTBS without premedication and motor activity resulted in a facilitation of MEPs 30 min after intervention, confirming previous observations. Conversely, cTBS induced depression of MEP size when subjects were premedicated with 30 mg of nimodipine. A short period of voluntary contraction (1.5 min) and a smaller dose of nimodipine (15 mg) were each ineffective in changing the polarity of cTBS-induced facilitation of corticospinal excitability. However, when both interventions were combined, a strong depression was induced. cTBS-induced potentiation of MEP-size was also abolished when subjects were under the influence of dextromethorphan, a blocker of Nmethyl-D-aspartate-receptors. Conclusions: Ca21 influx through L-type voltage-gated calcium channels may be an important factor underlying metaplasticity induced by endogenous neuronal activation.
rTMS Poster Only 195
High frequency repetitive transcranial magnetic stimulation induces a decrease of cerebral vasomotor reactivity
Melgari J1, Vernieri F1, Maggio P1, Tibuzzi F2, Filippi M2, Pasqualetti P3, Palazzo P1, Altamura C1, Rossini P1, 1University Campus Bio-Medico, Rome (Roma, IT); 2FBF-Isola Tiberina (Roma, IT); 3AFaRFBF-Isola Tiberina (Roma, IT) Objective: High frequency repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex of the stroke-affected hemisphere, was recently proposed as a potential treatment to facilitate functional recovery; however its effect on cerebral hemodynamics has not been exhaustively investigated. This study aims to examine the effects of high frequency rTMS on cerebral vasomotor reactivity (VMR), i.e. the potential of vessels to dilate following hypercapnic stimuli, measured by transcranial Doppler in the middle cerebral artery (MCA) territory. Method: Twenty-nine healthy subjects were selected: 19 were randomly assigned to real rTMS, 10 to sham rTMS. Repetitive TMS consisted of eight trains of 17-Hz stimulation lasting 3 seconds, with a rest period of 5 minutes between trains. The site of rTMS was the First Dorsal Interosseus ‘‘hot spot’’ of the dominant hemisphere and the intensity was 110% of the relaxed Motor Threshold. MFV was measured by TCD at rest condition and after inhalation of a mixture of 7% CO2/air. VMR was considered as the relative change in MFV after inhalation of this mixture. All subjects underwent a basal evaluation (T0) of mean flow velocity (MFV) and VMR bilaterally, one session of real or sham rTMS and a second evaluation of MFV and VMR (T1), within ten minutes from rTMS end. Four subjects underwent further MFV and VMR evaluations at 2, 5 and 24 hours from rTMS. Besides, 6 subjects underwent 17 Hz occipital rTMS at phospene threshold intensity. Results: Basal MFV did not change between pre and post rTMS evaluations. After real rTMS on M1, VMR significantly decreased
Abstracts
TMS Poster Only 191
Evoked motor response following deep transcranial magnetic stimulation in a cynomolgus monkey
Ishii K1, Matsuzaka Y2, Izumi S1, Abe T3, Nakazato N4, Okita T5, Yashima Y3, Takagi T5, Nagatomi R1, 1Tohoku university Graduate School of Biomedical Engineering (Sendai, JP); 2 Dept. of Physiol., Graduate Scool of Medical Sciences, Tohoku University (Sendai, JP); 3IFG Co., Ltd. (Sendai, JP); 4Kohnan Hospital (Sendai, JP); 5Institute of Fluid Science, Tohoku University (Sendai, JP) Objective: Transcranial magnetic stimulation (TMS) is a noninvasive technique in which magnetic pulses of the current loops are applied to the brain cortex. It is difficult to stimulate deeper regions of the brain with current TMS techniques, since the magnetic field strength decays in inverse proportion to the square of the distance from the current sources. We have recently developed a new TMS coil to overcome this limitation. The purpose of this study is, therefore, to show the new TMS coil is capable of stimulating deeper regions of the brain by monitoring the evoked motor responses and the silent periods following magnetic pulses delivered to the brain of a cynomolgus monkey. Method: A 5-year-old male cynomolgus monkey weighing 3.8kg was fixed on a primate chair, anesthetized with ketamine. Magnetic stimulus was delivered using a circular coil of 10 turns with internal diameters of 110 mm. The coil was set so that the head was inserted into the coil. The surface of the coil was set either at 0, 10, 20 or 30 mm below a plane including bilateral porus acusticus externus and supraorbital tori. A single electric pulse was applied to the coil at voltages ranging from 500 to 1000 V. The distribution of the pulsed magnetic flux density generated by the coil was numerically calculated with the use of RC integration circuit. Motor evoked potentials were recorded from the right triceps brachii muscle via intramuscular electrodes. The experiment was recorded with a video camera. Result: Fig.1 shows the distribution of the pulsed magnetic flux density generated by the coil. Fig.2. shows a representative electromyogram recording from the triceps brachii muscle, in which a silent period and a secondary response induced by the magnetic stimuli were recorded. Not only upper limb but also lower limb and trunk muscle contractions were elicited by the magnetic pulse. No acute adverse events such as hypotensive shock, epileptic seizure, visual and auditory impairment, and abnormal behaviors were observed. Conclusion: Using a newly designed TMS coil, we could successfully deliver magnetic stimuli to the brain of a cynomolgus monkey that evoked motor responses and silent periods. The fact that our TMS coil did not only elicit contraction of arm muscles, but also of lower limb muscles and trunk muscles, suggests that the new TMS technique is capable of efficiently stimulating deeper regions of the brain for the 1st time in the world.
Movement Disorders Poster Only 192
Cortical contribution to subthalamic activity during chronic electrical stimulation
Modolo J, Beuter A, IMS, UMR CNRS 5218 (Talence, FR) Objective: In Parkinson’s disease (PD), the motor cortex appears to play an important role in the generation of abnormal activity in the motor loop network involving basal ganglia, thalamus and cortex. When activity in this network is disrupted, motor symptoms appear but are alleviated by deep brain stimulation (DBS). We use a computational model to examine cortical contribution during DBS. Exploring brain mechanims underlying the effect of DBS may help us propose less invasive but efficient (cortical) stimulation protocols. Method: We used a multi-scale, population based, mathematical model of the subthalamic nucleus (STN) -the main excitatory structure of the basal ganglia- and the external globus pallidus, which receive cortical and striatal input. The model simulates healthy (stable, low-amplitude) and pathological (5 Hz oscillatory synchronized) activity within these two nuclei. In the pathological state, constant or oscillatory (low-frequency) cortical inputs to the STN are simulated and the ability of DBS to suppress abnormal oscillations (bursts) is explored. Results: In the presence of 10 Hz cortical inputs to the STN, DBS does not suppress abnormal bursts present in the STN and correlated with tremor generation (Figure 1). On the contrary DBS suppresses abnormal bursts when cortical input is constant (not shown).
Conclusion: Results support the view that a functional decoupling takes place between resonant cortical input and STN during DBS in PD. Indeed cortical input to the STN has a frequency similar to that of the STN, enhancing STN abnormal oscillatory behavior. This decoupling may originate from the descending cortical spikes colliding with the antidromic depolarization rising from the STN and induced by DBS. This mechanism could be responsible for clinical improvements. In principle such a
Abstracts functional decoupling may be achieved through cortical stimulation. This could be done in practice by switching from low- to high-pass the filter properties of cortical synapses, thus removing the low-frequency cortical contribution.
tDCS Poster Only 193
Improved deceptive skills by modulating activity in the prefrontal cortex
Fecteau S1, Boggio PS2, Ferreira M2, Pascual-Leone A1, Theoret H3, Fregni F1, Theoret H3, 1BIDMC, Harvard Medical School (, US); 2 Universidade Presbiteriana Mackenzie (Sao Paulo, BR); 3Universite de Montreal (Montreal, CA) From an evolutionary view, deception is among survival behaviors. In human, deceptive ability is crucial to survive and succeed in social situations. This ability appears early in human ontogenesis and follows the developmental course of intricate social communication behaviors. Management of deceptive signals requires knowledge of complex communication rules, such as understanding subtle modulation of facial expressions, vocal information at both linguistic and paralinguistic levels, and reflects efficiency of higher cognitive functions such as theory of mind. Without accurate deceptive ability, one is at risk of being socially vulnerable. For instance, individuals with autism who display social and communication difficulties often fail at understanding deception [1]. In regards to neurobiological foundation, deceptive behaviors elicit a complex neural network and are consistently associated with the prefrontal cortex with a right hemisphere dominance [1]. Activity in the right dorsolateral (DLPFC) and ventrolateral prefrontal cortex is enhanced when contrasting deceptive with truthful verbal or motor responses. Importantly, these activations have been correlated with response time; lengthened response time for deceptive answers is a robust effect [1]. Objective: This work aims at improving deceptive ability in healthy volunteers. Based on findings showing that deception elicits increased activity in the right DLPFC and longer response time, we hypothesized that enhancing activity in the right DLPFC will result in improved deceptive skills, that is decreased response time to produce untruthful answers. Method: We conducted a series of experiment using transcranial direct current stimulation to test this hypothesis. We applied concurrent anodal stimulation to the right DLPFC, known to enhance activity, with cathodal stimulation to the left DLPCF, which downregulates activity, to improve various spontaneous deceptive skills. Results: Volunteers displayed improved deceptive skills after receiving anodal stimulation to the right DLPFC coupled with cathodal to the left DLPFC. They were faster and more accurate than those who received the opposite active stimulation (anodal to the left DLPFC coupled with cathodal to the right DLPFC) and sham stimulation. Conclusion: The present results support the involvement of the DLPFC in deceptive behaviors and contribute to the understanding of social communication behaviors. 1.Spence SA et al. Phil Trans R Soc Lond B 2004
rTMS Poster Only 194
Metaplasticity of cTBS-induced enhancement of corticospinal excitability: Dependence on activation of L-Type voltage-gated Ca21 channels
Wankerl K, Gentner R, Weise D, Zeller D, Classen J, Universita¨t Wu¨rzburg (Wu¨rzburg, DE) Objective: Magnetic theta-burst stimulation (cTBS), a novel non-invasive repetitive magnetic stimulation protocol, modulates human corticospinal
301 excitability bidirectionally in dependence on prior motor activity, consistent with the notion of metaplasticity. However, the physiological foundations of this form of metaplasticity are unclear. Studies in slice preparations have identified Ca21 signalling as a possible underlying mechanism. Here we studied these effects with cTBS in combination with pharmacological interventions in vivo. Methods: In 10 subjects and different sessions, cTBS (50 Hz-bursts of three subtreshold magnetic stimuli repeated at 5 Hz) was applied for a duration of 20 sec after different combinations of premedication with nimodipine, an Ltype voltage gated Ca21 channel antagonist, and prior isometric motor activity of 0 min, 1.5 min and 5 min. Motor evoked potentials (MEPs) from the abductor pollicis brevis muscle were recorded before and within 30 min after intervention as an index of corticospinal excitability. Results: cTBS without premedication and motor activity resulted in a facilitation of MEPs 30 min after intervention, confirming previous observations. Conversely, cTBS induced depression of MEP size when subjects were premedicated with 30 mg of nimodipine. A short period of voluntary contraction (1.5 min) and a smaller dose of nimodipine (15 mg) were each ineffective in changing the polarity of cTBS-induced facilitation of corticospinal excitability. However, when both interventions were combined, a strong depression was induced. cTBS-induced potentiation of MEP-size was also abolished when subjects were under the influence of dextromethorphan, a blocker of Nmethyl-D-aspartate-receptors. Conclusions: Ca21 influx through L-type voltage-gated calcium channels may be an important factor underlying metaplasticity induced by endogenous neuronal activation.
rTMS Poster Only 195
High frequency repetitive transcranial magnetic stimulation induces a decrease of cerebral vasomotor reactivity
Melgari J1, Vernieri F1, Maggio P1, Tibuzzi F2, Filippi M2, Pasqualetti P3, Palazzo P1, Altamura C1, Rossini P1, 1University Campus Bio-Medico, Rome (Roma, IT); 2FBF-Isola Tiberina (Roma, IT); 3AFaRFBF-Isola Tiberina (Roma, IT) Objective: High frequency repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex of the stroke-affected hemisphere, was recently proposed as a potential treatment to facilitate functional recovery; however its effect on cerebral hemodynamics has not been exhaustively investigated. This study aims to examine the effects of high frequency rTMS on cerebral vasomotor reactivity (VMR), i.e. the potential of vessels to dilate following hypercapnic stimuli, measured by transcranial Doppler in the middle cerebral artery (MCA) territory. Method: Twenty-nine healthy subjects were selected: 19 were randomly assigned to real rTMS, 10 to sham rTMS. Repetitive TMS consisted of eight trains of 17-Hz stimulation lasting 3 seconds, with a rest period of 5 minutes between trains. The site of rTMS was the First Dorsal Interosseus ‘‘hot spot’’ of the dominant hemisphere and the intensity was 110% of the relaxed Motor Threshold. MFV was measured by TCD at rest condition and after inhalation of a mixture of 7% CO2/air. VMR was considered as the relative change in MFV after inhalation of this mixture. All subjects underwent a basal evaluation (T0) of mean flow velocity (MFV) and VMR bilaterally, one session of real or sham rTMS and a second evaluation of MFV and VMR (T1), within ten minutes from rTMS end. Four subjects underwent further MFV and VMR evaluations at 2, 5 and 24 hours from rTMS. Besides, 6 subjects underwent 17 Hz occipital rTMS at phospene threshold intensity. Results: Basal MFV did not change between pre and post rTMS evaluations. After real rTMS on M1, VMR significantly decreased