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Repeated stimulation of the posterior parietal cortex in patients in minimally conscious state: a sham-controlled randomized clinical trial
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Abstracts / Brain Stimulation 10 (2017) 346e540
Results: Twelve severely depressed inpatients (Age: mean 59.9 ± 13.9 years; Gender: 5 female (41.7%)) participated in the study. ECT reduced MADRS total score (before ECT: 30.6 ± 8.7; after ECT: 6.1 ± 6.4; t ¼ -8.88, p < .0001). ECT significantly increased effective connectivity from SCC to DLPFC (t ¼ 3.83, p ¼ 0.003), and decreased bidirectional effective connectivity between SCC and MTL (from SCC to MTL: t ¼ -4.79, p <0.001; from MTL to SCC: t ¼ -3.28, t ¼ 0.007). Conclusions: Our findings of this preliminary study indicated that ECT increased corticolimbic connectivity and reduced information flow within limbic regions, raising the possibility that electrophysiological approach might complement the findings of previous imaging studies investigating the mechanisms of ECT. Keywords: electroconvulsive therapy, electroencephalography, depressive disorder, Granger causality [0138] REDUCED SERUM LIPID LEVELS IN PATIENTS RECEIVING ECT PRELIMINARY FINDINGS A. Stautland 1, U. Kessler*2, L. Oltedal 1, 2, J. Haavik 2, 3, K.J. Oedegaard 1, 2. 1 University of Bergen, Norway; 2 Haukeland University Hospital, Norway; 3 K.G. Jebsen Centre for Neuropsychiatric Disorders, Norway Introduction: Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness. There is evidence for an altered lipid metabolism in MDD. Electroconvulsive therapy (ECT) is perhaps the most effective acute treatment of MDD. The mechanisms of action of ECT are not fully understood, but might include changes in lipid metabolism. The aim of the study was to assess changes in serum lipid concentrations in MDD patients undergoing ECT. The study is part of a larger, multidisciplinary trial investigating the mechanisms of ECT. Methods: Serum lipid levels were measured in 16 patients suffering from treatment resistant MDD using a non-targeted lipidomics approach. Blood samples were obtained before first treatment and approximately one week after the completed treatment series. Ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to detect lipid metabolites. A matched pairs t-test was used to compare pre and post-treatment samples. Results: In total, 399 lipid metabolites were detected, of which 69 were significantly altered after ECT. Post-treatment samples showed reduction of serum concentration in several classes of lipid metabolites, especially free fatty acids (FFA). Significant decreases were found in nearly all of the detected monoacylglycerol species, within several diacylglycerol species, several lysolipids and other phospholipid breakdown products and a number of fatty acid dicarboxylates. Discussion: The observed changes in lipid levels can be mediated by different processes, including changes in biosynthesis and breakdown rates of FFAs. This can be related to altered levels of exercise, distribution and storage of lipids or dietary changes. More investigations are needed to explore the contributions of these processes. The study contributes to elucidate the role of lipid metabolism in MDD and the effects of ECT. Further investigations in larger samples should be performed to confirm these results and evaluate the clinical significance of the findings. Keywords: Electroconvulsive Therapy, Treatment resistent MDD, Lipidomics, Lipids [0139] REPEATED STIMULATION OF THE POSTERIOR PARIETAL CORTEX IN PATIENTS IN MINIMALLY CONSCIOUS STATE: A SHAM-CONTROLLED RANDOMIZED CLINICAL TRIAL G. Martens*1, A. Thibaut 2,1, W. Huang 3, H. Di 3, S. Laureys 1. 1 University of Li ege, Belgium; 2 Harvard Medical School, USA; 3 Hangzhou Normal University, China Background: We assessed the effect of transcranial direct current stimulation (tDCS) targeted to posterior parietal cortex in patients in minimally conscious state (MCS). Methods: In a randomized double-blind sham-controlled crossover study, MCS patients at least 1 month after acute traumatic or nontraumatic insult received one sham and one real tDCS session (2mA during 20 minutes once a
day for five days) in a randomized order separated by five days of washout over the posterior parietal cortex. Coma Recovery Scale-Revised (CRS-R) assessments were performed directly on enrollment, before the first session and after each real and sham tDCS as well as five days later. Follow-up outcome data were acquired 1, 3, 6, 12 months after inclusion using the CRS-R. Results: 33 patients were included (interval 6±5 months; 20 traumatic). We found a treatment effect after 5 days of stimulation (p¼0.012; effect size: 0.31). The effect did not last for 5 days after the end of the stimulation (p¼0.135). We identified 9 (27%) tDCS-responders (i.e., showing new sign(s) of consciousness that was never observed before, lasting at least 5 days after the end of the stimulation). Conclusion: 5 days of tDCS over the posterior parietal cortex has a small and short-lasted beneficial effect on consciousness in MCS. Classification of Evidence: This study provides Class I evidence that 5 days of tDCS of the posterior parietal cortex has a small and short-lasted beneficial effect on consciousness in MCS. Clinical Trial register: ClinicalTrials.gov NCT02702362 Keywords: rtDCS, consciousness, posterior parietal cortex, minimally conscious state [0141] NEURAL CORRELATES OF CORTICOSPINAL EXCITABILITY OF THE DOMINANT HAND C. Rosso*1,2, V. Perlbarg 2, R. Valabregue 2, E. Moulton 2, S. Meunier 1, 2, J.C. ^pital Piti e-Salp^ etri ere, France; 2 Institut du cerveau et de la Lamy 2. 1 Ho moelle, France Introduction: Functional magnetic resonance imaging and transcranial magnetic stimulation are well-established tools used to probe distinct aspects of brain activity. However, the relationship between structural and functional variability of the sensorimotor system and corticospinal excitability levels, as indexed by the resting motor threshold (rMT), is poorly known. We used comprehensive multiple regression analyses to investigate associations between corticospinal excitability and measures of brain structure and function in the dominant hemisphere of healthy volunteers. Methods: Twenty-one subjects (mean±SD age: 35±13 years) underwent a multimodal MRI before the measurement of the rMT in the first dorsal interosseous muscle contralateral to the left dominant hemisphere. Correlation analyses were performed between rMT and anatomical measures of the grey matter (cortical volume), white matter (fractional anisotropy) of the following sensorimotor regions: dorsal premotor (PMd), primary motor (M1), and postcentral (S1) cortices, as well as the supplementary motor area. Resting state functional connectivity (FC) indexes between M1 and these regions, and between both M1, were determined. Surviving MRI measurements and age were entered in a stepwise multiple regression analysis to explain rMT levels. Results: Left rMT was inversely correlated with the FC between left PMd and M1 (r¼ -0.496, 95%CI: -0.764; -0.081; p¼0.02) and with the total left cortical volume (r¼ -0.463, 95%CI: -0.746; -0.039; p¼0.03). The multiple regression analysis retained the three following variables in the model: age (coefficient: -0.42±0.12), the FC between left PMd and M1 (coefficient: -25±7) and the left grey matter volume (coefficient: -0.297±0.064) explaining 66% of the variance of the rMT (p¼0.003). Discussion: This study shows that a simple TMS measure reflects, at least in part, the variability of anatomical and functional structures in the human brain. Indeed, our results highlight the major role of PMd and corticocortical connections toward M1 in the excitation of the corticospinal fibers through trans-synaptic pathways. Keywords: corticospinal excitability, resting state functional MRI [0142] FROM AURICULAR ACUPUNCTURE TO TRANSCUTANEOUS VAGAL NERVE STIMULATION (TVNS) T.I. Usichenko*1, 2. 1 McMaster University, Canada; 2 University of Greifswald, Germany Introduction: Although the neurophysiological background of transcutaneous vagal nerve stimulation (tVNS) is clear, the data about therapeutic effects is contradictory. The aim was to review the modern literature about basic mechanisms and clinical application of tVNS.
Abstracts / Brain Stimulation 10 (2017) 346e540
Results: Twelve severely depressed inpatients (Age: mean 59.9 ± 13.9 years; Gender: 5 female (41.7%)) participated in the study. ECT reduced MADRS total score (before ECT: 30.6 ± 8.7; after ECT: 6.1 ± 6.4; t ¼ -8.88, p < .0001). ECT significantly increased effective connectivity from SCC to DLPFC (t ¼ 3.83, p ¼ 0.003), and decreased bidirectional effective connectivity between SCC and MTL (from SCC to MTL: t ¼ -4.79, p <0.001; from MTL to SCC: t ¼ -3.28, t ¼ 0.007). Conclusions: Our findings of this preliminary study indicated that ECT increased corticolimbic connectivity and reduced information flow within limbic regions, raising the possibility that electrophysiological approach might complement the findings of previous imaging studies investigating the mechanisms of ECT. Keywords: electroconvulsive therapy, electroencephalography, depressive disorder, Granger causality [0138] REDUCED SERUM LIPID LEVELS IN PATIENTS RECEIVING ECT PRELIMINARY FINDINGS A. Stautland 1, U. Kessler*2, L. Oltedal 1, 2, J. Haavik 2, 3, K.J. Oedegaard 1, 2. 1 University of Bergen, Norway; 2 Haukeland University Hospital, Norway; 3 K.G. Jebsen Centre for Neuropsychiatric Disorders, Norway Introduction: Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness. There is evidence for an altered lipid metabolism in MDD. Electroconvulsive therapy (ECT) is perhaps the most effective acute treatment of MDD. The mechanisms of action of ECT are not fully understood, but might include changes in lipid metabolism. The aim of the study was to assess changes in serum lipid concentrations in MDD patients undergoing ECT. The study is part of a larger, multidisciplinary trial investigating the mechanisms of ECT. Methods: Serum lipid levels were measured in 16 patients suffering from treatment resistant MDD using a non-targeted lipidomics approach. Blood samples were obtained before first treatment and approximately one week after the completed treatment series. Ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to detect lipid metabolites. A matched pairs t-test was used to compare pre and post-treatment samples. Results: In total, 399 lipid metabolites were detected, of which 69 were significantly altered after ECT. Post-treatment samples showed reduction of serum concentration in several classes of lipid metabolites, especially free fatty acids (FFA). Significant decreases were found in nearly all of the detected monoacylglycerol species, within several diacylglycerol species, several lysolipids and other phospholipid breakdown products and a number of fatty acid dicarboxylates. Discussion: The observed changes in lipid levels can be mediated by different processes, including changes in biosynthesis and breakdown rates of FFAs. This can be related to altered levels of exercise, distribution and storage of lipids or dietary changes. More investigations are needed to explore the contributions of these processes. The study contributes to elucidate the role of lipid metabolism in MDD and the effects of ECT. Further investigations in larger samples should be performed to confirm these results and evaluate the clinical significance of the findings. Keywords: Electroconvulsive Therapy, Treatment resistent MDD, Lipidomics, Lipids [0139] REPEATED STIMULATION OF THE POSTERIOR PARIETAL CORTEX IN PATIENTS IN MINIMALLY CONSCIOUS STATE: A SHAM-CONTROLLED RANDOMIZED CLINICAL TRIAL G. Martens*1, A. Thibaut 2,1, W. Huang 3, H. Di 3, S. Laureys 1. 1 University of Li ege, Belgium; 2 Harvard Medical School, USA; 3 Hangzhou Normal University, China Background: We assessed the effect of transcranial direct current stimulation (tDCS) targeted to posterior parietal cortex in patients in minimally conscious state (MCS). Methods: In a randomized double-blind sham-controlled crossover study, MCS patients at least 1 month after acute traumatic or nontraumatic insult received one sham and one real tDCS session (2mA during 20 minutes once a
day for five days) in a randomized order separated by five days of washout over the posterior parietal cortex. Coma Recovery Scale-Revised (CRS-R) assessments were performed directly on enrollment, before the first session and after each real and sham tDCS as well as five days later. Follow-up outcome data were acquired 1, 3, 6, 12 months after inclusion using the CRS-R. Results: 33 patients were included (interval 6±5 months; 20 traumatic). We found a treatment effect after 5 days of stimulation (p¼0.012; effect size: 0.31). The effect did not last for 5 days after the end of the stimulation (p¼0.135). We identified 9 (27%) tDCS-responders (i.e., showing new sign(s) of consciousness that was never observed before, lasting at least 5 days after the end of the stimulation). Conclusion: 5 days of tDCS over the posterior parietal cortex has a small and short-lasted beneficial effect on consciousness in MCS. Classification of Evidence: This study provides Class I evidence that 5 days of tDCS of the posterior parietal cortex has a small and short-lasted beneficial effect on consciousness in MCS. Clinical Trial register: ClinicalTrials.gov NCT02702362 Keywords: rtDCS, consciousness, posterior parietal cortex, minimally conscious state [0141] NEURAL CORRELATES OF CORTICOSPINAL EXCITABILITY OF THE DOMINANT HAND C. Rosso*1,2, V. Perlbarg 2, R. Valabregue 2, E. Moulton 2, S. Meunier 1, 2, J.C. ^pital Piti e-Salp^ etri ere, France; 2 Institut du cerveau et de la Lamy 2. 1 Ho moelle, France Introduction: Functional magnetic resonance imaging and transcranial magnetic stimulation are well-established tools used to probe distinct aspects of brain activity. However, the relationship between structural and functional variability of the sensorimotor system and corticospinal excitability levels, as indexed by the resting motor threshold (rMT), is poorly known. We used comprehensive multiple regression analyses to investigate associations between corticospinal excitability and measures of brain structure and function in the dominant hemisphere of healthy volunteers. Methods: Twenty-one subjects (mean±SD age: 35±13 years) underwent a multimodal MRI before the measurement of the rMT in the first dorsal interosseous muscle contralateral to the left dominant hemisphere. Correlation analyses were performed between rMT and anatomical measures of the grey matter (cortical volume), white matter (fractional anisotropy) of the following sensorimotor regions: dorsal premotor (PMd), primary motor (M1), and postcentral (S1) cortices, as well as the supplementary motor area. Resting state functional connectivity (FC) indexes between M1 and these regions, and between both M1, were determined. Surviving MRI measurements and age were entered in a stepwise multiple regression analysis to explain rMT levels. Results: Left rMT was inversely correlated with the FC between left PMd and M1 (r¼ -0.496, 95%CI: -0.764; -0.081; p¼0.02) and with the total left cortical volume (r¼ -0.463, 95%CI: -0.746; -0.039; p¼0.03). The multiple regression analysis retained the three following variables in the model: age (coefficient: -0.42±0.12), the FC between left PMd and M1 (coefficient: -25±7) and the left grey matter volume (coefficient: -0.297±0.064) explaining 66% of the variance of the rMT (p¼0.003). Discussion: This study shows that a simple TMS measure reflects, at least in part, the variability of anatomical and functional structures in the human brain. Indeed, our results highlight the major role of PMd and corticocortical connections toward M1 in the excitation of the corticospinal fibers through trans-synaptic pathways. Keywords: corticospinal excitability, resting state functional MRI [0142] FROM AURICULAR ACUPUNCTURE TO TRANSCUTANEOUS VAGAL NERVE STIMULATION (TVNS) T.I. Usichenko*1, 2. 1 McMaster University, Canada; 2 University of Greifswald, Germany Introduction: Although the neurophysiological background of transcutaneous vagal nerve stimulation (tVNS) is clear, the data about therapeutic effects is contradictory. The aim was to review the modern literature about basic mechanisms and clinical application of tVNS.