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Does peripheral vagus nerve impairment affect biochemical composition of dopamine-related brain regions?
Abstracts / Brain Stimulation 8 (2015) 343e359
Single transcranial magnetic stimulation (TMS) is widely used for studying the excitability of cerebral structures. Apart from the generation of motor evoked potentials (MEPs), a suprathreshold single pulse focal TMS may induce selective contralateral movements. The relationship between MEPs and TMS-induced movement is unknown, but it is reasonable to expect that movements correlate with MEP size in the agonist muscle. We determined the relationship between MEPs in the wrist extensors (WE) and the wrist flexors (WF) and the movement induced in the wrist by TMS in healthy subjects. Methods: Subjects were sitting with their right forearm and hand tightly fixed on a two-pieces metallic platform joined with a hinge allowing only for flexo/extension wrist movements. TMS was applied over the contralateral motor area. Movements induced on the wrist joint were recorded with a built-in signal transducer that was entered, together with the EMG activity from the WE and WF muscles, into a polygraphic recording system (Biopac Systems, Spain). Subjects were studied at rest and in positions of 30o of wrist flexion or extension maintained either passively or voluntarily. Mild isometric contractions towards flexion and extension were also studied. Results: MEPs at rest were larger in the WE than in the WF. However, the movements induced were more frequently towards flexion than towards extension. MEPs were facilitated in the muscle shortened with passive or active holding of the position. Maximum voluntary contraction towards flexion induced movements at latency shorter than when contraction was done towards extension. In the latter, movement towards flexion appeared to occur at latency compatible with the TMS-induced silent period. Conclusions: TMS-induced wrist movement depends only in part on the size of the MEPs evoked in WE and WF. The larger proportion of flexion movements may be due to asymmetric muscle elastic properties and stretch reflex gain.
158 Medial temporal lobe stimulation may disrupt contextdependent memory retrieval M.B. Merkow a, J.F. Burke b, A.R. Ramayya b, A. Sharan c, M.J. Kahana d, M.R. Sperling e a Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, 19104, USA b Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104, USA c Department of Neurosurgery, Thomas Jefferson University Hospitals, 19107, USA c Department of Psychology, University of Pennsylvania, 19104, USA e Department of Neurology, Thomas Jefferson University Hospitals, 19107, USA Direct brain stimulation is a potential method to alter cognition. Recently, it has been shown that current applied to the entorhinal cortex enhances spatial memory (Suthana et al., 2012). We tested the hypothesis that medial temporal lobe stimulation modulates verbal memory, and that this effect is dependent on the phase of memory processing. 5 left-language dominant patients (2 women, age 19-57) undergoing intracranial monitoring for intractable epilepsy participated in our delayed free-recall stimulation paradigm (8 unique stimulation sites; mean 3.8 mA and 20.9 uC/cm2/phase). Medial temporal lobe stimulation decreased recall performance (t-test, t7¼2.34, p ¼ 0.003) and was modulated by the timing of its delivery (encoding, distractor, retrieval periods; ANOVA, F23,2 ¼ 6.75, p ¼ 0.009). Recall memory was most impaired during distractor period stimulation
355
(distractor vs. encoding, t7 ¼ 2.53, p ¼ 0.039; distractor vs. retrieval, t7 ¼ 3.78, p ¼ 0.007). Moreover, response times showed the same pattern: distractor stimulation slowed time to first word recall more than retrieval stimulation (t7 ¼ 2.86, p ¼ 0.024). We interpret these results as evidence that medial temporal lobe stimulation either impairs rehearsal of list items during the delay between encoding and recall or disrupts the neural correlates of temporal context, thereby impairing one’s ability to the use the current contextual state as a retrieval cue. While our results may represent causal support for context-dependent retrieval memory theories, further research is necessary to distinguish these two possibilities. Moreover, future studies are necessary to map memory function with medial temporal lobe stimulation and to use this technique to treat memory disorders in the clinical setting.
159 Does peripheral vagus nerve impairment affect biochemical composition of dopamine-related brain regions? A.D. Surowka a, A. Krygowska-Wajs b, A. Ziomber c, P. Thor c, A.A. Chrobak d, M. Szczerbowska-Boruchowska a a AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow, Poland b Department of Neurology, Jagiellonian University Collegium Medicum, Krakow, Poland c Department of Pathophysiology, Jagiellonian University Collegium Medicum, Krakow, Poland c Jagiellonian University Neurology Students’ Club, Jagiellonian University, Medical College, Krakow, Poland Introduction: Dorsal motor nucleus of the vagus nerve (VN) is being recognized as a point of departure of early-stage changes related to a gradual development of pathologies in dopaminergic system. Studies indicates it is likely that the biochemical changes occurring within a peripheral nervous system could influence a physiology of the dopaminergic system, suggesting it’s putative role in the development of neurodegenerative disorders. The aim of our study is to evaluate whether chronic VN could influence a biochemical composition of dopamine-related brain structures. Methods: Twelve male Wistar rats were subjected to surgical implantation of the microchip in the abdominal region of the left VN. 6 rats underwent microchip stimulation, while 6 underwent shamlaparotomy. Rats were stimulated for 7 days, with period of the stimulating signal equal to 20 seconds, duration of 0.1s, and amplitude of 200mV. By using FTIR spectroscopy we examined the effect of chronic, unilateral electrical VN stimulation on changes in the lipid composition, and in the protein secondary structure within the dopamine-related brain structures in rats. Results: Chronic VN stimulation strongly affects fatty acids chain length within ventral tegemental area, nucleus accumbens, subtantia nigra, striatum, dorsal motor nucleus of vagus, and motor cortex. Level of lipid unsaturation was found to be significantly increased in ventral tegemental area, subtantia nigra and motor cortex as a result of VN impairment. In protein secondary structure mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by VN stimulation due to the co-occurrence of statistically significant changes in the content of all: non-ordered structure components, alpha-helices, beta sheets and in the total area of the Amide I. Discussion: The observed macromolecular changes caused by the peripheral VN impairment, may highlight the potential connection between the gastrointestinal system and the central nervous system in rat, which could occur during development of neurodegenerative disorders.
Single transcranial magnetic stimulation (TMS) is widely used for studying the excitability of cerebral structures. Apart from the generation of motor evoked potentials (MEPs), a suprathreshold single pulse focal TMS may induce selective contralateral movements. The relationship between MEPs and TMS-induced movement is unknown, but it is reasonable to expect that movements correlate with MEP size in the agonist muscle. We determined the relationship between MEPs in the wrist extensors (WE) and the wrist flexors (WF) and the movement induced in the wrist by TMS in healthy subjects. Methods: Subjects were sitting with their right forearm and hand tightly fixed on a two-pieces metallic platform joined with a hinge allowing only for flexo/extension wrist movements. TMS was applied over the contralateral motor area. Movements induced on the wrist joint were recorded with a built-in signal transducer that was entered, together with the EMG activity from the WE and WF muscles, into a polygraphic recording system (Biopac Systems, Spain). Subjects were studied at rest and in positions of 30o of wrist flexion or extension maintained either passively or voluntarily. Mild isometric contractions towards flexion and extension were also studied. Results: MEPs at rest were larger in the WE than in the WF. However, the movements induced were more frequently towards flexion than towards extension. MEPs were facilitated in the muscle shortened with passive or active holding of the position. Maximum voluntary contraction towards flexion induced movements at latency shorter than when contraction was done towards extension. In the latter, movement towards flexion appeared to occur at latency compatible with the TMS-induced silent period. Conclusions: TMS-induced wrist movement depends only in part on the size of the MEPs evoked in WE and WF. The larger proportion of flexion movements may be due to asymmetric muscle elastic properties and stretch reflex gain.
158 Medial temporal lobe stimulation may disrupt contextdependent memory retrieval M.B. Merkow a, J.F. Burke b, A.R. Ramayya b, A. Sharan c, M.J. Kahana d, M.R. Sperling e a Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, 19104, USA b Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104, USA c Department of Neurosurgery, Thomas Jefferson University Hospitals, 19107, USA c Department of Psychology, University of Pennsylvania, 19104, USA e Department of Neurology, Thomas Jefferson University Hospitals, 19107, USA Direct brain stimulation is a potential method to alter cognition. Recently, it has been shown that current applied to the entorhinal cortex enhances spatial memory (Suthana et al., 2012). We tested the hypothesis that medial temporal lobe stimulation modulates verbal memory, and that this effect is dependent on the phase of memory processing. 5 left-language dominant patients (2 women, age 19-57) undergoing intracranial monitoring for intractable epilepsy participated in our delayed free-recall stimulation paradigm (8 unique stimulation sites; mean 3.8 mA and 20.9 uC/cm2/phase). Medial temporal lobe stimulation decreased recall performance (t-test, t7¼2.34, p ¼ 0.003) and was modulated by the timing of its delivery (encoding, distractor, retrieval periods; ANOVA, F23,2 ¼ 6.75, p ¼ 0.009). Recall memory was most impaired during distractor period stimulation
355
(distractor vs. encoding, t7 ¼ 2.53, p ¼ 0.039; distractor vs. retrieval, t7 ¼ 3.78, p ¼ 0.007). Moreover, response times showed the same pattern: distractor stimulation slowed time to first word recall more than retrieval stimulation (t7 ¼ 2.86, p ¼ 0.024). We interpret these results as evidence that medial temporal lobe stimulation either impairs rehearsal of list items during the delay between encoding and recall or disrupts the neural correlates of temporal context, thereby impairing one’s ability to the use the current contextual state as a retrieval cue. While our results may represent causal support for context-dependent retrieval memory theories, further research is necessary to distinguish these two possibilities. Moreover, future studies are necessary to map memory function with medial temporal lobe stimulation and to use this technique to treat memory disorders in the clinical setting.
159 Does peripheral vagus nerve impairment affect biochemical composition of dopamine-related brain regions? A.D. Surowka a, A. Krygowska-Wajs b, A. Ziomber c, P. Thor c, A.A. Chrobak d, M. Szczerbowska-Boruchowska a a AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow, Poland b Department of Neurology, Jagiellonian University Collegium Medicum, Krakow, Poland c Department of Pathophysiology, Jagiellonian University Collegium Medicum, Krakow, Poland c Jagiellonian University Neurology Students’ Club, Jagiellonian University, Medical College, Krakow, Poland Introduction: Dorsal motor nucleus of the vagus nerve (VN) is being recognized as a point of departure of early-stage changes related to a gradual development of pathologies in dopaminergic system. Studies indicates it is likely that the biochemical changes occurring within a peripheral nervous system could influence a physiology of the dopaminergic system, suggesting it’s putative role in the development of neurodegenerative disorders. The aim of our study is to evaluate whether chronic VN could influence a biochemical composition of dopamine-related brain structures. Methods: Twelve male Wistar rats were subjected to surgical implantation of the microchip in the abdominal region of the left VN. 6 rats underwent microchip stimulation, while 6 underwent shamlaparotomy. Rats were stimulated for 7 days, with period of the stimulating signal equal to 20 seconds, duration of 0.1s, and amplitude of 200mV. By using FTIR spectroscopy we examined the effect of chronic, unilateral electrical VN stimulation on changes in the lipid composition, and in the protein secondary structure within the dopamine-related brain structures in rats. Results: Chronic VN stimulation strongly affects fatty acids chain length within ventral tegemental area, nucleus accumbens, subtantia nigra, striatum, dorsal motor nucleus of vagus, and motor cortex. Level of lipid unsaturation was found to be significantly increased in ventral tegemental area, subtantia nigra and motor cortex as a result of VN impairment. In protein secondary structure mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by VN stimulation due to the co-occurrence of statistically significant changes in the content of all: non-ordered structure components, alpha-helices, beta sheets and in the total area of the Amide I. Discussion: The observed macromolecular changes caused by the peripheral VN impairment, may highlight the potential connection between the gastrointestinal system and the central nervous system in rat, which could occur during development of neurodegenerative disorders.