- Email: [email protected]
Characterisation of glutamatergic and GABAA mediated neurotransmission in motor and dorsolateral prefrontal cortex using paired-pulse TMS-EEG
502
Abstracts / Brain Stimulation 10 (2017) 346e540
Conclusions: Our preliminary results provide evidence that cathodal tDCS is a safe treatment approach for epilepsy. It will not increase the seizure frequency during the treatment session, and may potentially reduce the epileptiform discharges and slow waves. There may be temporarily negative effect on short-term memory, with no evidence of change in other cognitive functions. Long-term follow-up is needed for further study. Keywords: epilepsy, cognitive, tDCS [0640] ARTIFICIAL INDUCTION OF CORTICAL PLASTICITY BY HIGH FREQUENCY CORTICAL STIMULATION PERMITS TO INCREASE RESECTION OF BRAIN TUMORS LOCATED IN ELOQUENT AREAS rez. Hospital Clínico San J.A. Barcia*, C. Nombela, J. Matías-Guiu, M. Pe Carlos, Spain Extent of resection is the main factor in the prognosis of WHO grade 2 and 3 gliomas. This is limited by the presence of eloquent areas near or within the tumor. However, if those functions could be artificially displaced away from the tumor, a greater extent of resection could be feasible. We present 5 cases of gliomas localized at eloquent areas (one anaplasic astrocytoma at Broca’s area, one left frontal oligodendroglioma, one left temporoparietal anaplasic oligodendroglioma at Wernicke’s area, one anaplasic astrocytoma at the primary motor area, and one left frontal astrocytoma compromising Broca’s and primary motor area).These patients were operated awake and the tumors could not be resected according to established cortical stimulation standards. A cortical grid of electrodes was placed over the tumor and inhibitory continuous stimulation (130 Hz, 60 us) was continuously applied to the grid’s functional contacts. The intensity was set daily to the threshold of inducing a mild functional deficit, while the patient performed an intensive rehabilitation of the function. When an intensity of 10 mA was achieved in all active contacts producing none deficit (usually after 3 weeks), the patients were reoperated. This procedure permitted an extended resection of the tumor. Functional studies showed a displacement of the functions to other locations in neighboring areas or at the contralateral hemisphere. We present evidence of artificial enhancement of plasticity by HFCS in tumors containing eloquent areas, permitting an extensive resection, maintaining the functions and improving the survival and quality of life of the patients. Keywords: Glioma surgery, eloquent cortical areas, brain plasticity, cortical brain stimulation [0643] MAGNETIC SEIZURE THERAPY COMPARED TO ECT IN MAJOR DEPRESSIVE DISORDER: A MEDICATION-FREE CLINICAL CONTROLLED TRIAL F.A. El-Deeb 1, E.A. Gad 1, A.A. Kandeel 2, A.A. Haiba 1, S.M. Sadek 1, N.A. Youssef*3. 1 Tanta University, Egypt; 2 Cairo University, Egypt; 3 Medical College of Georgia at Augusta University, USA Objective: The aims of this study were to 1) Evaluate the feasibility and safety of magnetic seizure therapy (MST) in treating major depressive disorder (MDD) in the Egyptian population. 2) compare the efficacy of MST in MDD to that of ECT; 3) compare the cognitive adverse effects of MST to that of ECT. Methods: After IRB approval and informed consent, patients indicated for ECT from 18-65 years of age and who were not on antidepressant treatment for 6 weeks were assigned to 2 groups to be treated with either MST or ECT. After anaesthesia and muscle relaxation patient received either RUL or BL ECT with Thymatron IV (Somatics, Venice, FL, USA) and pulse width of 0.5msec, or HD-MST with Magstim Theta device (Wales, UK) at the Psychiatry, Neurology and Neurosurgery Center, Tanta University, Egypt. The MST stimulation was at 100% of device output, frequency 100Hz, and train duration of 10 seconds at vertex placement. Treatments were applied twice a week. Efficacy was primarily assessed by Hamilton Depression Scale-21 (HAM-D-21) and cognitive side effects were assessed by Time to Reorientation (TRO) and a neuropsychological battery (pre-post course). Brain SPECT was done for 10 patients pre-post MST course to explore biological changes associated with MST. Results: Sixty depressed patients with MDD (DSM-IV) were enrolled in this study (thirty males and thirty females). There was no difference in
depression improvement between MST and ECT group. In addition, MST had significantly less cognitive adverse effects and much faster TRO of 1.8min (SD¼0.36) compared to ECT. SPECT generally showed Improvements of areas of hypoperfusion seen before MST course. Conclusion: MST was feasible and safe in this population. It was also efficacious in treating MDD with less cognitive adverse effects than ECT. Larger studies are needed to replicate these findings before adoption in clinical care. Keywords: Magnetic Seizure Therapy (MST), Electroconvulsive Therapy (ECT), Major depressive disorder, SPECT [0644] INFLUENCE OF THE BDNF VAL66MET POLYMORPHISM ON THE BALANCE OF EXCITATORY AND INHIBITORY NEUROTRANSMISSION AND RELATIONSHIP TO PLASTICITY IN HUMAN CORTEX R. Cash*1, 3, K. Udupa 1, C. Gunraj 1, F. Mazzella 1, Z.J. Daskalakis 2, A.H. Wong 2, J.L. Kennedy 2, P.B. Fitzgerald 3, R. Chen 1. 1 Toronto Western Research Institute, Canada; 2 Centre for Addiction and Mental Health, Canada; 3 Monash Alfred Psychiatry Research Centre, Australia Introduction: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) is associated with different plasticity responses, the influence of BDNF genotype on neural circuitries and relationship to neuroplasticity remain unexplored in human. Methods: 9 Val homozygotes and 9 Met allele carriers were recruited. The following circuits were investigated: GABAA receptor mediated short interval intracortical inhibition (SICI), GABAB receptor mediated long interval intracortical inhibition (LICI) and an excitatory circuit termed short interval intracortical facilitation (SICF). Results: SICI and LICI were consistently stronger in Val/Val compared to Met allele carriers. SICF ISI curves differed strikingly between groups: maximum SICF was greater in Val/Val compared to Met carriers, while there was little difference at the SICF trough. RMT did not differ between groups. There was a tightly regulated excitatory and inhibitory (E/I) balance, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like forms of phase dependent I-wave (ITMS) plasticity, which is related to the excitatory SICF circuit, were greater in Val/Val homozygotes. LTP- but not LTD-like effects could be restored in Met allele carriers by increasing stimulus intensity during ITMS to compensate for reduced SICF. Discussion: These findings indicate that the influence of BDNF in human extends beyond neuroplasticity to fundamental neural circuit properties, and that deficits in plasticity induction may be related to deficits in excitatory synaptic transmission. Adjustment of stimulus parameters depending of genotype may be needed to achieve benefit in therapeutic repetitive transcranial magnetic stimulation protocols. The findings indicate that that a balance between the strength of excitatory and inhibitory circuits is a feature of human motor cortex and open a new line of inquiry for the non-invasive investigation of this balance in neurological disorders. Keywords: BDNF, Balance, Inhibition, ITMS [0645] CHARACTERISATION OF GLUTAMATERGIC AND GABAA MEDIATED NEUROTRANSMISSION IN MOTOR AND DORSOLATERAL PREFRONTAL CORTEX USING PAIRED-PULSE TMS-EEG R. Cash*4,5, Y. Noda 1, 3, R. Zomorrodi 1, N. Radhu 1, 4, F. Farzan 1, T.K. Rajji 1, 2, R. Chen 4, Z.J. Daskalakis 1, 2, P.B. Fitzgerald 5, D.M. Blumberger 1, 2. 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Canada; 2 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; 3 University of Toronto, Canada; 4 Toronto Western Research Institute, Canada; 5 Monash Alfred Psychiatry Research Centre, Australia Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are non-invasive transcranial magnetic stimulation (TMS) measures of GABAA receptor mediated inhibition and glutamatergic excitatory transmission respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from dorsolateral prefrontal cortex (DLPFC) using combined TMS and
Abstracts / Brain Stimulation 10 (2017) 346e540
electroencephalography (TMSeEEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS evoked potentials (TEPs) and spectral power modulation. Subsequently these paradigms were applied in DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation respectively) of P30 and P60 TEP amplitude which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, while P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing non-invasive measures of glutamatergic and GABAA receptor mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders. Keywords: TMS-EEG, SICI, ICF, DLPFC [0648] CONTINUOUS THETA-BURST STIMULATION OF MEDIAL PREFRONTAL CORTEX ENHANCES SCHEMA-LINKED ENCODING A.N. Vorobiova*1, A.A. Shpektor 1, 2, M. Feurra 1. 1 National Research University Higher School of Economics, Russia; 2 University of Oxford, UK Introduction: It has long been established that the existence of prior knowledge (or schema representation) to which new information can be related, facilitates memory encoding, consolidation and retrieval. Schema is interpreted as a network of strongly interrelated neocortical representations. Recent studies show the role of the medial prefrontal cortex (mPFC) for establishing a link between representations of objects based on their congruency to either prior knowledge or to each other, thereby facilitating memory functions. Methods: We used MRI-navigated continuous theta-burst stimulation (cTBS) delivered over the mPFC to modulate encoding of object-scene paired associations at different levels of congruency (i.e. differently fitting to subject’s knowledge about real world). Stimulation was applied by using a novel parabolic-shaped focal coil that allows deeper brain stimulation than conventional one. Sham and conventional stimulation were included as controls. The next day subjects were asked to perform a stimulation-free retrieval memory task. Results: We found that mPFC-cTBS, delivered before encoding, selectively increased memory retrieval performance (item recognition and associative memory) only for congruent items (compared to incongruent and intermediate) with respect to stimulation controls. Discussion: Our findings represent the first causal evidence on the role of mPFC in associative memory. The effect is condition-specific and well controlled. The facilitatory effect of cTBS is likely to be due to the intrinsic inhibitory mechanisms of mPFC towards the medial temporal lobe (MTL) which also play a role in consolidation processes of congruent associations. Keywords: associative memory, schema, medial prefrontal cortex, continuous theta-burst stimulation [0650] HUMAN ACUTE NEUROPHYSIOLOGICAL RESPONSES TO MAGNETICALLY-INDUCED ALTERNATING CURRENT DENSITIES OF UP TO 100 MA.M-2 A. Legros*1, 2, J. Modolo 3,1, M. Corbacio 1, S. Davarpanah Jazi 1, S. Villard 1, D. Goulet 4, M. Plante 4, M. Souques 5, F. Deschamps 6, G. Ostiguy 4. 1 LHRI and e de Montpellier, France; Western University, Canada; 2 EuroMov, Universit 3 INSERM, France; 4 Hydro-Qu ebec, Canada; 5 EDF, France; 6 RTE, France Introduction: Living in our modern environment implies that we are constantly subjected to various types of electromagnetic exposures coming from different artificial sources, such as mobile phones, power-lines or electrical appliances. As a consequence, the question of possible biological effects from this type of exposure arises, and international organizations such as ICNIRP (International Commission on Non-Ionizing Radiation Protection) and IEEE-ICES (Institute of Electrical and Electronics Engineers
503
- International Committee on Electromagnetic Safety) are responsible for issuing limits and recommendations to ensure public health and worker safety. In the context of the so-called Extremely Low Frequencies (ELF, <300 Hz), the time-varying magnetic field (MF) from the exposure induces electric fields and currents within biological structures, possibly leading to biological effects including on neuronal functions. In this frequency range, limits and recommendations are based on the exposure threshold at which acute effects are observed on synaptic communication in humans, hence resulting in modulated functional outcomes. Methods: Our team is working since 2005 towards experimentally establishing these thresholds in human through the study of magnetically induced cognitive (e.g. short term memory) or motor (e.g. tremor, postural stability) modulations, changes in functional brain activity, and acute visual perceptions called magnetophosphenes. Results: This presentation will give an overview of recent human studies investigating the impact of ELF exposures on neurophysiological outcomes, and will report new results establishing the threshold for an acute neurophysiological response in humans: magnetophosphene perception. Conclusion: Knowing and understanding the implications of this threshold for an acute neurophysiological response to a time-varying MF is critical from an international guidelines standpoint. Also, since the induced electric fields and current densities resulting from such stimuli are comparable to those produced by tDCS and tACS, possible translational applications will be discussed. Keywords: Magnetophosphenes, Human study, Extremely Low Frequency Magnetic Field, Threshold effect [0655] TRANSCRANIAL ALTERNATING CURRENT STIMULATION FOR BOOSTING CORTICOSPINAL EXCITABILITY AND RESTITUTION OF INTRACORTICAL INHIBITION IN ELDERLY M. Christova*1, 2, S. Fresnoza 3, E. Gallasch 1, A. Ischebeck 3. 1 Medical University of Graz, Austria; 2 University of Applied Sciences Graz, Austria; 3 University of Graz, Austria The oscillatory alpha-band activity (8-12 Hz) reflects the GABAergic inhibition that blocks task irrelevant activity, thereby increasing the signal-tonoise ratio within the brain networks. In aging, there is a parallel decrease in alpha activity and GABA- mediated inhibitory processes with a profound effect on cognitive abilities. Application of transcranial alternating current stimulation (tACS) was shown to modulate brain oscillation, cortical excitability and behaviour. EEG studies suggest a state dependent effect of tACS: upregulation of alpha oscillations only in conditions of low prestimulation alpha power. Therefore, tACS might be especially useful in elderly with reduced alpha power. To explore the state/age-dependent effect of tACS on cortical excitability, tACS at individual alpha frequency (IAF) with 1.5 mA current was applied to the left motor cortex of 12 young and 12 old volunteers for 10min. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to assess the corticospinal and intracortical excitability changes immediately, 1h and 2h post tACS. The results showed age/state-dependent effect of tACS applied at IAF on motor cortical excitability. Stimulation among elderly individuals with slower oscillation and less alpha power caused a significant increase in corticospinal excitability at lower TMS intensities and GABA-mediated intracortical inhibition after tACS. Younger participants with higher oscillation frequency and alpha power showed significant increase in corticospinal excitability at higher TMS intensities only, while intracortical inhibition and facilitation were not affected. The study compares for the first time the after effect of tACS at IAF on the cortical excitability of younger and elderly brain. Data further add on the growing evidence that the tACS effect is dependent on the alpha activity state before stimulation. tACS can be considered as a promising tool that can safely modulate oscillatory activity for studying brain functions and can be given as an individualized treatment regimen for patients. [0659] VAGUS NERVE STIMULATION THERAPY FOR CHRONIC MEDICAL DISORDERS L.L. Carpenter*1, 2. 1 Butler Hospital, USA; 2 Brown University, USA
Abstracts / Brain Stimulation 10 (2017) 346e540
Conclusions: Our preliminary results provide evidence that cathodal tDCS is a safe treatment approach for epilepsy. It will not increase the seizure frequency during the treatment session, and may potentially reduce the epileptiform discharges and slow waves. There may be temporarily negative effect on short-term memory, with no evidence of change in other cognitive functions. Long-term follow-up is needed for further study. Keywords: epilepsy, cognitive, tDCS [0640] ARTIFICIAL INDUCTION OF CORTICAL PLASTICITY BY HIGH FREQUENCY CORTICAL STIMULATION PERMITS TO INCREASE RESECTION OF BRAIN TUMORS LOCATED IN ELOQUENT AREAS rez. Hospital Clínico San J.A. Barcia*, C. Nombela, J. Matías-Guiu, M. Pe Carlos, Spain Extent of resection is the main factor in the prognosis of WHO grade 2 and 3 gliomas. This is limited by the presence of eloquent areas near or within the tumor. However, if those functions could be artificially displaced away from the tumor, a greater extent of resection could be feasible. We present 5 cases of gliomas localized at eloquent areas (one anaplasic astrocytoma at Broca’s area, one left frontal oligodendroglioma, one left temporoparietal anaplasic oligodendroglioma at Wernicke’s area, one anaplasic astrocytoma at the primary motor area, and one left frontal astrocytoma compromising Broca’s and primary motor area).These patients were operated awake and the tumors could not be resected according to established cortical stimulation standards. A cortical grid of electrodes was placed over the tumor and inhibitory continuous stimulation (130 Hz, 60 us) was continuously applied to the grid’s functional contacts. The intensity was set daily to the threshold of inducing a mild functional deficit, while the patient performed an intensive rehabilitation of the function. When an intensity of 10 mA was achieved in all active contacts producing none deficit (usually after 3 weeks), the patients were reoperated. This procedure permitted an extended resection of the tumor. Functional studies showed a displacement of the functions to other locations in neighboring areas or at the contralateral hemisphere. We present evidence of artificial enhancement of plasticity by HFCS in tumors containing eloquent areas, permitting an extensive resection, maintaining the functions and improving the survival and quality of life of the patients. Keywords: Glioma surgery, eloquent cortical areas, brain plasticity, cortical brain stimulation [0643] MAGNETIC SEIZURE THERAPY COMPARED TO ECT IN MAJOR DEPRESSIVE DISORDER: A MEDICATION-FREE CLINICAL CONTROLLED TRIAL F.A. El-Deeb 1, E.A. Gad 1, A.A. Kandeel 2, A.A. Haiba 1, S.M. Sadek 1, N.A. Youssef*3. 1 Tanta University, Egypt; 2 Cairo University, Egypt; 3 Medical College of Georgia at Augusta University, USA Objective: The aims of this study were to 1) Evaluate the feasibility and safety of magnetic seizure therapy (MST) in treating major depressive disorder (MDD) in the Egyptian population. 2) compare the efficacy of MST in MDD to that of ECT; 3) compare the cognitive adverse effects of MST to that of ECT. Methods: After IRB approval and informed consent, patients indicated for ECT from 18-65 years of age and who were not on antidepressant treatment for 6 weeks were assigned to 2 groups to be treated with either MST or ECT. After anaesthesia and muscle relaxation patient received either RUL or BL ECT with Thymatron IV (Somatics, Venice, FL, USA) and pulse width of 0.5msec, or HD-MST with Magstim Theta device (Wales, UK) at the Psychiatry, Neurology and Neurosurgery Center, Tanta University, Egypt. The MST stimulation was at 100% of device output, frequency 100Hz, and train duration of 10 seconds at vertex placement. Treatments were applied twice a week. Efficacy was primarily assessed by Hamilton Depression Scale-21 (HAM-D-21) and cognitive side effects were assessed by Time to Reorientation (TRO) and a neuropsychological battery (pre-post course). Brain SPECT was done for 10 patients pre-post MST course to explore biological changes associated with MST. Results: Sixty depressed patients with MDD (DSM-IV) were enrolled in this study (thirty males and thirty females). There was no difference in
depression improvement between MST and ECT group. In addition, MST had significantly less cognitive adverse effects and much faster TRO of 1.8min (SD¼0.36) compared to ECT. SPECT generally showed Improvements of areas of hypoperfusion seen before MST course. Conclusion: MST was feasible and safe in this population. It was also efficacious in treating MDD with less cognitive adverse effects than ECT. Larger studies are needed to replicate these findings before adoption in clinical care. Keywords: Magnetic Seizure Therapy (MST), Electroconvulsive Therapy (ECT), Major depressive disorder, SPECT [0644] INFLUENCE OF THE BDNF VAL66MET POLYMORPHISM ON THE BALANCE OF EXCITATORY AND INHIBITORY NEUROTRANSMISSION AND RELATIONSHIP TO PLASTICITY IN HUMAN CORTEX R. Cash*1, 3, K. Udupa 1, C. Gunraj 1, F. Mazzella 1, Z.J. Daskalakis 2, A.H. Wong 2, J.L. Kennedy 2, P.B. Fitzgerald 3, R. Chen 1. 1 Toronto Western Research Institute, Canada; 2 Centre for Addiction and Mental Health, Canada; 3 Monash Alfred Psychiatry Research Centre, Australia Introduction: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) is associated with different plasticity responses, the influence of BDNF genotype on neural circuitries and relationship to neuroplasticity remain unexplored in human. Methods: 9 Val homozygotes and 9 Met allele carriers were recruited. The following circuits were investigated: GABAA receptor mediated short interval intracortical inhibition (SICI), GABAB receptor mediated long interval intracortical inhibition (LICI) and an excitatory circuit termed short interval intracortical facilitation (SICF). Results: SICI and LICI were consistently stronger in Val/Val compared to Met allele carriers. SICF ISI curves differed strikingly between groups: maximum SICF was greater in Val/Val compared to Met carriers, while there was little difference at the SICF trough. RMT did not differ between groups. There was a tightly regulated excitatory and inhibitory (E/I) balance, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like forms of phase dependent I-wave (ITMS) plasticity, which is related to the excitatory SICF circuit, were greater in Val/Val homozygotes. LTP- but not LTD-like effects could be restored in Met allele carriers by increasing stimulus intensity during ITMS to compensate for reduced SICF. Discussion: These findings indicate that the influence of BDNF in human extends beyond neuroplasticity to fundamental neural circuit properties, and that deficits in plasticity induction may be related to deficits in excitatory synaptic transmission. Adjustment of stimulus parameters depending of genotype may be needed to achieve benefit in therapeutic repetitive transcranial magnetic stimulation protocols. The findings indicate that that a balance between the strength of excitatory and inhibitory circuits is a feature of human motor cortex and open a new line of inquiry for the non-invasive investigation of this balance in neurological disorders. Keywords: BDNF, Balance, Inhibition, ITMS [0645] CHARACTERISATION OF GLUTAMATERGIC AND GABAA MEDIATED NEUROTRANSMISSION IN MOTOR AND DORSOLATERAL PREFRONTAL CORTEX USING PAIRED-PULSE TMS-EEG R. Cash*4,5, Y. Noda 1, 3, R. Zomorrodi 1, N. Radhu 1, 4, F. Farzan 1, T.K. Rajji 1, 2, R. Chen 4, Z.J. Daskalakis 1, 2, P.B. Fitzgerald 5, D.M. Blumberger 1, 2. 1 Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Canada; 2 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; 3 University of Toronto, Canada; 4 Toronto Western Research Institute, Canada; 5 Monash Alfred Psychiatry Research Centre, Australia Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are non-invasive transcranial magnetic stimulation (TMS) measures of GABAA receptor mediated inhibition and glutamatergic excitatory transmission respectively. Conventionally these measures have been restricted to the motor cortex. We investigated whether SICI and ICF could be recorded from dorsolateral prefrontal cortex (DLPFC) using combined TMS and
Abstracts / Brain Stimulation 10 (2017) 346e540
electroencephalography (TMSeEEG). We first characterized the neural signature of SICI and ICF in M1 in terms of TMS evoked potentials (TEPs) and spectral power modulation. Subsequently these paradigms were applied in DLPFC to determine whether similar neural signatures were evident. With TMS at M1, SICI and ICF led to bidirectional modulation (inhibition and facilitation respectively) of P30 and P60 TEP amplitude which correlated with MEP amplitude changes. With DLPFC stimulation, P60 was bidirectionally modulated by SICI and ICF in the same manner as for M1 stimulation, while P30 was absent. The sole modulation of early TEP components is in contradistinction to other measures such as long interval intracortical inhibition and may reflect modulation of short latency excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs). Overall the data suggest that SICI and ICF can be recorded using TMS-EEG in DLPFC providing non-invasive measures of glutamatergic and GABAA receptor mediated neurotransmission. This may facilitate future research attempting to ascertain the role of these neurotransmitters in the pathophysiology and treatment of neurological and psychiatric disorders. Keywords: TMS-EEG, SICI, ICF, DLPFC [0648] CONTINUOUS THETA-BURST STIMULATION OF MEDIAL PREFRONTAL CORTEX ENHANCES SCHEMA-LINKED ENCODING A.N. Vorobiova*1, A.A. Shpektor 1, 2, M. Feurra 1. 1 National Research University Higher School of Economics, Russia; 2 University of Oxford, UK Introduction: It has long been established that the existence of prior knowledge (or schema representation) to which new information can be related, facilitates memory encoding, consolidation and retrieval. Schema is interpreted as a network of strongly interrelated neocortical representations. Recent studies show the role of the medial prefrontal cortex (mPFC) for establishing a link between representations of objects based on their congruency to either prior knowledge or to each other, thereby facilitating memory functions. Methods: We used MRI-navigated continuous theta-burst stimulation (cTBS) delivered over the mPFC to modulate encoding of object-scene paired associations at different levels of congruency (i.e. differently fitting to subject’s knowledge about real world). Stimulation was applied by using a novel parabolic-shaped focal coil that allows deeper brain stimulation than conventional one. Sham and conventional stimulation were included as controls. The next day subjects were asked to perform a stimulation-free retrieval memory task. Results: We found that mPFC-cTBS, delivered before encoding, selectively increased memory retrieval performance (item recognition and associative memory) only for congruent items (compared to incongruent and intermediate) with respect to stimulation controls. Discussion: Our findings represent the first causal evidence on the role of mPFC in associative memory. The effect is condition-specific and well controlled. The facilitatory effect of cTBS is likely to be due to the intrinsic inhibitory mechanisms of mPFC towards the medial temporal lobe (MTL) which also play a role in consolidation processes of congruent associations. Keywords: associative memory, schema, medial prefrontal cortex, continuous theta-burst stimulation [0650] HUMAN ACUTE NEUROPHYSIOLOGICAL RESPONSES TO MAGNETICALLY-INDUCED ALTERNATING CURRENT DENSITIES OF UP TO 100 MA.M-2 A. Legros*1, 2, J. Modolo 3,1, M. Corbacio 1, S. Davarpanah Jazi 1, S. Villard 1, D. Goulet 4, M. Plante 4, M. Souques 5, F. Deschamps 6, G. Ostiguy 4. 1 LHRI and e de Montpellier, France; Western University, Canada; 2 EuroMov, Universit 3 INSERM, France; 4 Hydro-Qu ebec, Canada; 5 EDF, France; 6 RTE, France Introduction: Living in our modern environment implies that we are constantly subjected to various types of electromagnetic exposures coming from different artificial sources, such as mobile phones, power-lines or electrical appliances. As a consequence, the question of possible biological effects from this type of exposure arises, and international organizations such as ICNIRP (International Commission on Non-Ionizing Radiation Protection) and IEEE-ICES (Institute of Electrical and Electronics Engineers
503
- International Committee on Electromagnetic Safety) are responsible for issuing limits and recommendations to ensure public health and worker safety. In the context of the so-called Extremely Low Frequencies (ELF, <300 Hz), the time-varying magnetic field (MF) from the exposure induces electric fields and currents within biological structures, possibly leading to biological effects including on neuronal functions. In this frequency range, limits and recommendations are based on the exposure threshold at which acute effects are observed on synaptic communication in humans, hence resulting in modulated functional outcomes. Methods: Our team is working since 2005 towards experimentally establishing these thresholds in human through the study of magnetically induced cognitive (e.g. short term memory) or motor (e.g. tremor, postural stability) modulations, changes in functional brain activity, and acute visual perceptions called magnetophosphenes. Results: This presentation will give an overview of recent human studies investigating the impact of ELF exposures on neurophysiological outcomes, and will report new results establishing the threshold for an acute neurophysiological response in humans: magnetophosphene perception. Conclusion: Knowing and understanding the implications of this threshold for an acute neurophysiological response to a time-varying MF is critical from an international guidelines standpoint. Also, since the induced electric fields and current densities resulting from such stimuli are comparable to those produced by tDCS and tACS, possible translational applications will be discussed. Keywords: Magnetophosphenes, Human study, Extremely Low Frequency Magnetic Field, Threshold effect [0655] TRANSCRANIAL ALTERNATING CURRENT STIMULATION FOR BOOSTING CORTICOSPINAL EXCITABILITY AND RESTITUTION OF INTRACORTICAL INHIBITION IN ELDERLY M. Christova*1, 2, S. Fresnoza 3, E. Gallasch 1, A. Ischebeck 3. 1 Medical University of Graz, Austria; 2 University of Applied Sciences Graz, Austria; 3 University of Graz, Austria The oscillatory alpha-band activity (8-12 Hz) reflects the GABAergic inhibition that blocks task irrelevant activity, thereby increasing the signal-tonoise ratio within the brain networks. In aging, there is a parallel decrease in alpha activity and GABA- mediated inhibitory processes with a profound effect on cognitive abilities. Application of transcranial alternating current stimulation (tACS) was shown to modulate brain oscillation, cortical excitability and behaviour. EEG studies suggest a state dependent effect of tACS: upregulation of alpha oscillations only in conditions of low prestimulation alpha power. Therefore, tACS might be especially useful in elderly with reduced alpha power. To explore the state/age-dependent effect of tACS on cortical excitability, tACS at individual alpha frequency (IAF) with 1.5 mA current was applied to the left motor cortex of 12 young and 12 old volunteers for 10min. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to assess the corticospinal and intracortical excitability changes immediately, 1h and 2h post tACS. The results showed age/state-dependent effect of tACS applied at IAF on motor cortical excitability. Stimulation among elderly individuals with slower oscillation and less alpha power caused a significant increase in corticospinal excitability at lower TMS intensities and GABA-mediated intracortical inhibition after tACS. Younger participants with higher oscillation frequency and alpha power showed significant increase in corticospinal excitability at higher TMS intensities only, while intracortical inhibition and facilitation were not affected. The study compares for the first time the after effect of tACS at IAF on the cortical excitability of younger and elderly brain. Data further add on the growing evidence that the tACS effect is dependent on the alpha activity state before stimulation. tACS can be considered as a promising tool that can safely modulate oscillatory activity for studying brain functions and can be given as an individualized treatment regimen for patients. [0659] VAGUS NERVE STIMULATION THERAPY FOR CHRONIC MEDICAL DISORDERS L.L. Carpenter*1, 2. 1 Butler Hospital, USA; 2 Brown University, USA