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Clinical benefits of electroconvulsive therapy for depressed patients with refractory complex regional pain syndrome (CRPS) type 1: A preliminary result
394
Abstracts / Brain Stimulation 10 (2017) 346e540
Introduction: Theta burst stimulation (TBS) can alter cortical excitability, similar to standard repetitive transcranial magnetic stimulation paradigms, with a major advantage of shorter stimulation duration at a lower intensity. There is increasing interest in the use of TBS as a therapeutic tool for disorders such as depression and schizophrenia, where prefrontal cortex is the primary target for treatment. In developing clinical applications for such psychiatric illnesses, there is a need to explore effects of different parameters of TBS in this region. This study aimed to examine the effects of different intensities of intermittent TBS (iTBS) on cortical reactivity in the prefrontal cortex. We hypothesized that iTBS would show greater cortical effects at sub-threshold intensities. Methods: 16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% rMT in separate sessions. Single pulse TMS-EEG was used to assess change in cortical reactivity via TMS-evoked potentials and TMS-evoked oscillations before and after iTBS. Results: Cluster-based statistics revealed a significant increase in N100 amplitude following 50% (p ¼ 0.011) and 75% (p ¼ 0.010) iTBS over prefrontal regions. No significant change was observed with 100% iTBS. Between conditions, the iTBS-induced change in N100 was larger following 75% compared to 100% iTBS (p ¼ 0.008). For oscillations, change in TMSevoked theta (p ¼ 0.027) and gamma power (p ¼ 0.006) were larger following 75% compared to 100% iTBS (figure below). No significant differences were observed between 50% and 75% iTBS, or 50% and 100% iTBS.
Ă
Discussion: Intensity of the stimulation should be carefully considered when administering TBS in the prefrontal cortex, as it may reduce iTBSinduced changes in cortical reactivity at or above individual’s motor threshold. This study may aid in optimising stimulation paradigm prior to the conduct of clinical trials. Keywords: theta burst stimulation (TBS), TMS-EEG, prefrontal cortex, intensity
[0233] RTMS IN DEPRESSION - ACCELERATING RESPONSE TO THERAPY P.B. Fitzgerald*. Monash University, Australia Purpose: Repetitive transcranial magnetic stimulation (rTMS) is now a well-established new treatment modality for patients with depressive disorders that has been assessed across a large range of controlled studies. However, response to treatment is typically slow and standard courses require 4 to 6 weeks of treatment sessions conducted five days per week, a practical burden for many patients. There is increasing interest in the development of high dose and accelerated treatment protocols although few studies to date have compared accelerated and standard methods of TMS administration. Methods: We have conducted a randomised controlled trial comparing a standard daily rTMS course over four weeks to an accelerated course of TMS treatment involving the same overall dose of therapy applied during three days in week one, two days in week two and one day week three. Results: No difference in treatment outcome was found between accelerated and the standard forms of rTMS treatment. There was a slightly higher dropout rate in the accelerated group but no marked difference in overall treatment tolerability. Anecdotally, accelerated treatment was extremely popular with patients.
Conclusions: There is emerging evidence that rTMS for patients with depression can be successfully applied in novel schedules over shorter periods of time. Accelerated treatment approaches have potential to make access to TMS more flexible and practical for some patients Keywords: depression, rTMS, accelerated, trial
[0234] DIFFERENT ROLES OF PRE-SMA AND SMA IN HUMAN VISUOMOTOR SEQUENCE LEARNING: A TMS STUDY T. Shimizu*1, 2, R. Hanajima 1, R. Tsutsumi 1, Y. Shirota 2, N. Tanaka 2, M. Hamada 2, Y. Ugawa 3. 1 Kitasato Medical University, Japan; 2 University of Tokyo, Japan; 3 Fukushima Medical University, Japan Introduction: Both the pre-supplementary motor area (pre-SMA) and the supplementary motor area proper (SMA) are known to take part in the visuomotor sequence learning. Previous reports implicated that the preSMA plays a role especially in the acquisition of a new sequence, while the SMA in movement itself rather than learning. Here we studied the roles of pre-SMA or SMA in human visuomotor sequence learning with repetitive transcranial magnetic stimulation technique. Methods: Sixteen healthy volunteers participated in this experiment. We applied Quadripulse transcranial magnetic stimulation (QPS) or sham stimulation over the left pre-SMA or SMA for 30 minutes. QPS consisted of repeated bursts of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms (QPS-5) or 50 ms (QPS-50) with an inter-burst interval of 5 s. After QPS, each subject performed the 210 task, which is similar to the visuomotor sequential task reported by Hikosaka et al. For performance evaluation, we counted the number of errors to assess the performance accuracy, and measured the movement time (MT) and button press reaction time (BP-RT) and obtained their acceleration, to assess the performance speed. Results: The number of errors was larger after QPS-5 over the pre-SMA compared to sham stimulation, whereas it did not differ between QPS-50 and sham conditions. In contrast, the number of errors did not differ between any stimulus conditions in SMA stimulation. Acceleration of BP-RT was enhanced after QPS-50 over the SMA and inhibited after QPS-5 over the SMA. In contrast, acceleration of BP-RT did not differ between any stimulus conditions in the pre-SMA stimulation. Discussion: Our findings suggested that the pre-SMA plays an important role in the acquisition of visuomotor sequence, whereas the SMA plays an important role in automatization of sequential movements. Keywords: transcranial magnetic stimulation, Quadripulse stimulation, sequence learning, supplementary motor area [0235] CLINICAL BENEFITS OF ELECTROCONVULSIVE THERAPY FOR DEPRESSED PATIENTS WITH REFRACTORY COMPLEX REGIONAL PAIN SYNDROME (CRPS) TYPE 1: A PRELIMINARY RESULT T.S. Kim*, H.J. Park, Y.H. Kim, D.E. Moon. The Catholic University of Korea, Republic of Korea Background: Complex regional pain syndrome (CRPS) is a chronic condition that has spontaneous severe pain and hyperesthesia of one or more parts of legs and arms, which is accompanied with problems of the automatic nervous system or the motor nervous system. It is often treatment-refractory and is frequently accompanied by depressive disorder. Electroconvulsive therapy (ECT) is a well-established treatment option for treatment-resistant depression and has also been applied in the treatment of chronic pain. In this open study, we investigated the efficacy of ECT in refractory depressed patient with CRPS type 1. Methods: Eight depressed patients (M¼4; F¼4) presenting CRPS type 1, who were treatment-refractory though treated with the best medical and psychiatric medication, were participated and had a total of 8 sessions of ECT three times a week. Pain intensity was assessed using Visual Analogue Scale (VAS) at baseline and endpoint (4 weeks) and after each session. Hamilton Depression Rating Scale (HDRS), Beck Scale for Suicide Ideation (SSI), Insomnia Severity Index (ISI), and Euro-QoL-5D (EQ-5D) were respectively measured for depression, suicide, insomnia, and quality of life at baseline and endpoint.
Abstracts / Brain Stimulation 10 (2017) 346e540
395
Results: There was a reduction in the VAS scores from baseline to endpoint, but it had a marginal statistical significance (p¼0.061). Compared to baseline, significant improvements in HDRS (p¼0.001), SSI (p¼0.014), ISI (p¼0.010), and EQ-5D (p¼0.023) scores were shown respectively at endpoint. The treatment was generally well tolerated. Headache and nausea were common adverse effects. Only one patient was dropped out due to memory loss. Conclusion: Although these are preliminary findings in an open trial, this study shows a possible efficacy of ECT for the treatment-refractory depressed patient with CRPS type 1. Adequate sample size will be warranted to confirm these clinical benefits. Keywords: electroconvulsive therapy, complex regional pain syndrome, depression, quality of life
retinotopic coordinates. V1 TMS affected temporal discrimination of stimuli presented in the lower left visual quadrant whereas V5/MT TMS the discrimination of stimuli presented in both the upper and the lower left visual quadrants. These results show that both V1 and V5/MT encode visual temporal information in retinotopic spatial frames, but the representation of time is quadrant specific for V1 and hemifield specific for V5/ MT. These results represent the first neurophysiological evidence of a link between space and time in human visual cortex. Keywords: Time, Space, paired-pulse TMS
[0237] TRANSCUTANEOUS VAGAL NERVE STIMULATION TO PROMOTE THE EXTINCTION OF FEAR
W. Wiratman*1, 2, T. Murakami 1, S. Kobayashi 1, H. Enomoto 1, Y. Ugawa 1. 1 Fukushima Medical University, Japan; 2 Universitas Indonesia, Indonesia
B. Verkuil 1, A.M. Burger*1, I. van Diest 2, B. Vervliet 3, W. van der Does 1, J.F. Thayer 4, J.F. Brosschot 1. 1 Leiden University, The Netherlands; 2 KU Leuven, Belgium; 3 Harvard Medical School, USA; 4 The Ohio State University, USA
Background: Repeated bursts of four monophasic TMS pulses (QPS) are known to induce long-term depression (LTD) in the motor cortex (M1) when the interstimulus interval is 50ms (QPSLTD, homosynaptic plasticity). It is also known that paired associative stimulation (PAS), a combination of monophasic TMS over the M1 and electric stimulation of the peripheral nerve, induces LTD or long-term potentiation (LTP), depending on the interpair interval (PASLTD at N20-5ms and PASLTP at N20+2ms; heterosynaptic plasticity). Objective: To investigate how the motor cortical excitability is modulated by combining QPS and PAS. Methods: Nine healthy subjects were examined with three intervention protocols; simple QPSLTD, combined PASLTD-QPSLTD, and combined PASLTPQPSLTD applied to the M1. We measured TMS-elicited motor evoked potentials (MEPs) before and after the intervention up to 60 minutes. First, we conducted one-way ANOVA (time) to find the effective time window of each intervention. To compare the effects of different interventions, we then applied one-way ANOVA (intervention) to the MEPs averaged in the defined time window. Results: ANOVA (time) showed a significant main effect (p<0.05). Post-hoc tests revealed significant MEP depression after QPSLTD (10 to 40, and 60 minutes) and PASLTD-QPSLTD (10 to 60 minutes). PASLTP-QPSLTD induced no significant MEP changes. ANOVA (intervention) applied to the mean MEPs in the effective time window showed a significant main effect (p<0.01). PASLTD-QPSLTD depressed MEPs to a greater degree than the other interventions (p<0.05). QPSLTD induced significantly greater depression than PASLTP-QPSLTD (p<0.05).
Introduction: A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve (VNS) has been proposed to enhance extinction memory through the increase of noradrenergic transmission. Method: We conducted two studies (N ¼ 38 & N ¼ 41) to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess fear conditioning and subsequent fear extinction, we assessed US expectancy ratings, fear potentiated startle responses and skin conductance levels. After fear conditioning, participants were randomly assigned to receive tVNS or sham stimulation during the extinction phase (study 1: extinction directly followed acquisition; study 2: extinction followed 24 hours later). Retention of extinction memory was tested 24 hours later. Results: In both studies, tVNS accelerated explicit fear extinction (US expectancy ratings). In study 2, spontaneous recovery for the skin conductance response occurred only in the sham group, but no differences were observed for the other outcomes during retention. Discussion: These findings support the hypothesis that tVNS accelerates declarative extinction learning. The findings are preliminary but consistent with recent studies that indicate that tVNS may be a tool to improve fear extinction. Keywords: transcutaneous vagus nerve stimulation, fear extinction, memory, anxiety
[0240] PAIRED ASSOCIATIVE QUADRIPULSE STIMULATION (PAS-QPS) - A NEW PROTOCOL COMBINING HOMO- AND HETERO-SYNAPTIC PLASTICITY
[0239] THE SPATIAL REPRESENTATION OF TIME IN VISUAL CORTEX nel-Pierre 2, M.M. Murray 2, D. Bueti 1. 1 International G. Fortunato*1, T. Ke School for Advanced Studies (SISSA), Neuroscience Area, Italy; 2 University Hospital of Lausanne, Switzerland Performing a timed movement like dancing, playing a musical instrument or simply walking requires for the brain the integration of both temporal and spatial information. How and where the human brain synergistically links these two types of information remains unclear. Previous studies have shown that primary visual cortex (V1) and extrastriate visual area V5/ MT are both involved in the encoding of temporal information of visual stimuli. However these studies do not clarify how time is encoded in these areas and whether V1 and V5/MT encode time differently. Here we tested the hypothesis that V1 and V5/MT encode time in different spatial coordinates, i.e. head-centred versus eye-centred. To this purpose we asked healthy volunteers to perform a temporal discrimination task of visual stimuli that were presented at varying combinations of retinotopic and head-centred spatiotopic positions. While participants were engaged in this task we interfered with the activity of the right dorsal V1 and the right V5/MT by mean of paired-pulse Transcranial Magnetic Stimulation (ppTMS). The results showed that ppTMS over both areas impaired temporal discrimination thresholds of visual stimuli presented at different
ĂDiscussion: When we combined the LTD-inducing PAS and the LTDinducing QPS, the depressive effects on MEP were additive. In contrast, when we combined the LTP-inducing PAS and LTD-inducing QPS, plasticity effects cancelled out. The combination protocol turned out to be a powerful method to induce MEP changes, which presumably involves physiologically distinct processes of homo- and hetero-synaptic plasticity. Keywords: heterosynaptic plasticity, homosynaptic plasticity, LTD, QPS
Abstracts / Brain Stimulation 10 (2017) 346e540
Introduction: Theta burst stimulation (TBS) can alter cortical excitability, similar to standard repetitive transcranial magnetic stimulation paradigms, with a major advantage of shorter stimulation duration at a lower intensity. There is increasing interest in the use of TBS as a therapeutic tool for disorders such as depression and schizophrenia, where prefrontal cortex is the primary target for treatment. In developing clinical applications for such psychiatric illnesses, there is a need to explore effects of different parameters of TBS in this region. This study aimed to examine the effects of different intensities of intermittent TBS (iTBS) on cortical reactivity in the prefrontal cortex. We hypothesized that iTBS would show greater cortical effects at sub-threshold intensities. Methods: 16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% rMT in separate sessions. Single pulse TMS-EEG was used to assess change in cortical reactivity via TMS-evoked potentials and TMS-evoked oscillations before and after iTBS. Results: Cluster-based statistics revealed a significant increase in N100 amplitude following 50% (p ¼ 0.011) and 75% (p ¼ 0.010) iTBS over prefrontal regions. No significant change was observed with 100% iTBS. Between conditions, the iTBS-induced change in N100 was larger following 75% compared to 100% iTBS (p ¼ 0.008). For oscillations, change in TMSevoked theta (p ¼ 0.027) and gamma power (p ¼ 0.006) were larger following 75% compared to 100% iTBS (figure below). No significant differences were observed between 50% and 75% iTBS, or 50% and 100% iTBS.
Ă
Discussion: Intensity of the stimulation should be carefully considered when administering TBS in the prefrontal cortex, as it may reduce iTBSinduced changes in cortical reactivity at or above individual’s motor threshold. This study may aid in optimising stimulation paradigm prior to the conduct of clinical trials. Keywords: theta burst stimulation (TBS), TMS-EEG, prefrontal cortex, intensity
[0233] RTMS IN DEPRESSION - ACCELERATING RESPONSE TO THERAPY P.B. Fitzgerald*. Monash University, Australia Purpose: Repetitive transcranial magnetic stimulation (rTMS) is now a well-established new treatment modality for patients with depressive disorders that has been assessed across a large range of controlled studies. However, response to treatment is typically slow and standard courses require 4 to 6 weeks of treatment sessions conducted five days per week, a practical burden for many patients. There is increasing interest in the development of high dose and accelerated treatment protocols although few studies to date have compared accelerated and standard methods of TMS administration. Methods: We have conducted a randomised controlled trial comparing a standard daily rTMS course over four weeks to an accelerated course of TMS treatment involving the same overall dose of therapy applied during three days in week one, two days in week two and one day week three. Results: No difference in treatment outcome was found between accelerated and the standard forms of rTMS treatment. There was a slightly higher dropout rate in the accelerated group but no marked difference in overall treatment tolerability. Anecdotally, accelerated treatment was extremely popular with patients.
Conclusions: There is emerging evidence that rTMS for patients with depression can be successfully applied in novel schedules over shorter periods of time. Accelerated treatment approaches have potential to make access to TMS more flexible and practical for some patients Keywords: depression, rTMS, accelerated, trial
[0234] DIFFERENT ROLES OF PRE-SMA AND SMA IN HUMAN VISUOMOTOR SEQUENCE LEARNING: A TMS STUDY T. Shimizu*1, 2, R. Hanajima 1, R. Tsutsumi 1, Y. Shirota 2, N. Tanaka 2, M. Hamada 2, Y. Ugawa 3. 1 Kitasato Medical University, Japan; 2 University of Tokyo, Japan; 3 Fukushima Medical University, Japan Introduction: Both the pre-supplementary motor area (pre-SMA) and the supplementary motor area proper (SMA) are known to take part in the visuomotor sequence learning. Previous reports implicated that the preSMA plays a role especially in the acquisition of a new sequence, while the SMA in movement itself rather than learning. Here we studied the roles of pre-SMA or SMA in human visuomotor sequence learning with repetitive transcranial magnetic stimulation technique. Methods: Sixteen healthy volunteers participated in this experiment. We applied Quadripulse transcranial magnetic stimulation (QPS) or sham stimulation over the left pre-SMA or SMA for 30 minutes. QPS consisted of repeated bursts of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms (QPS-5) or 50 ms (QPS-50) with an inter-burst interval of 5 s. After QPS, each subject performed the 210 task, which is similar to the visuomotor sequential task reported by Hikosaka et al. For performance evaluation, we counted the number of errors to assess the performance accuracy, and measured the movement time (MT) and button press reaction time (BP-RT) and obtained their acceleration, to assess the performance speed. Results: The number of errors was larger after QPS-5 over the pre-SMA compared to sham stimulation, whereas it did not differ between QPS-50 and sham conditions. In contrast, the number of errors did not differ between any stimulus conditions in SMA stimulation. Acceleration of BP-RT was enhanced after QPS-50 over the SMA and inhibited after QPS-5 over the SMA. In contrast, acceleration of BP-RT did not differ between any stimulus conditions in the pre-SMA stimulation. Discussion: Our findings suggested that the pre-SMA plays an important role in the acquisition of visuomotor sequence, whereas the SMA plays an important role in automatization of sequential movements. Keywords: transcranial magnetic stimulation, Quadripulse stimulation, sequence learning, supplementary motor area [0235] CLINICAL BENEFITS OF ELECTROCONVULSIVE THERAPY FOR DEPRESSED PATIENTS WITH REFRACTORY COMPLEX REGIONAL PAIN SYNDROME (CRPS) TYPE 1: A PRELIMINARY RESULT T.S. Kim*, H.J. Park, Y.H. Kim, D.E. Moon. The Catholic University of Korea, Republic of Korea Background: Complex regional pain syndrome (CRPS) is a chronic condition that has spontaneous severe pain and hyperesthesia of one or more parts of legs and arms, which is accompanied with problems of the automatic nervous system or the motor nervous system. It is often treatment-refractory and is frequently accompanied by depressive disorder. Electroconvulsive therapy (ECT) is a well-established treatment option for treatment-resistant depression and has also been applied in the treatment of chronic pain. In this open study, we investigated the efficacy of ECT in refractory depressed patient with CRPS type 1. Methods: Eight depressed patients (M¼4; F¼4) presenting CRPS type 1, who were treatment-refractory though treated with the best medical and psychiatric medication, were participated and had a total of 8 sessions of ECT three times a week. Pain intensity was assessed using Visual Analogue Scale (VAS) at baseline and endpoint (4 weeks) and after each session. Hamilton Depression Rating Scale (HDRS), Beck Scale for Suicide Ideation (SSI), Insomnia Severity Index (ISI), and Euro-QoL-5D (EQ-5D) were respectively measured for depression, suicide, insomnia, and quality of life at baseline and endpoint.
Abstracts / Brain Stimulation 10 (2017) 346e540
395
Results: There was a reduction in the VAS scores from baseline to endpoint, but it had a marginal statistical significance (p¼0.061). Compared to baseline, significant improvements in HDRS (p¼0.001), SSI (p¼0.014), ISI (p¼0.010), and EQ-5D (p¼0.023) scores were shown respectively at endpoint. The treatment was generally well tolerated. Headache and nausea were common adverse effects. Only one patient was dropped out due to memory loss. Conclusion: Although these are preliminary findings in an open trial, this study shows a possible efficacy of ECT for the treatment-refractory depressed patient with CRPS type 1. Adequate sample size will be warranted to confirm these clinical benefits. Keywords: electroconvulsive therapy, complex regional pain syndrome, depression, quality of life
retinotopic coordinates. V1 TMS affected temporal discrimination of stimuli presented in the lower left visual quadrant whereas V5/MT TMS the discrimination of stimuli presented in both the upper and the lower left visual quadrants. These results show that both V1 and V5/MT encode visual temporal information in retinotopic spatial frames, but the representation of time is quadrant specific for V1 and hemifield specific for V5/ MT. These results represent the first neurophysiological evidence of a link between space and time in human visual cortex. Keywords: Time, Space, paired-pulse TMS
[0237] TRANSCUTANEOUS VAGAL NERVE STIMULATION TO PROMOTE THE EXTINCTION OF FEAR
W. Wiratman*1, 2, T. Murakami 1, S. Kobayashi 1, H. Enomoto 1, Y. Ugawa 1. 1 Fukushima Medical University, Japan; 2 Universitas Indonesia, Indonesia
B. Verkuil 1, A.M. Burger*1, I. van Diest 2, B. Vervliet 3, W. van der Does 1, J.F. Thayer 4, J.F. Brosschot 1. 1 Leiden University, The Netherlands; 2 KU Leuven, Belgium; 3 Harvard Medical School, USA; 4 The Ohio State University, USA
Background: Repeated bursts of four monophasic TMS pulses (QPS) are known to induce long-term depression (LTD) in the motor cortex (M1) when the interstimulus interval is 50ms (QPSLTD, homosynaptic plasticity). It is also known that paired associative stimulation (PAS), a combination of monophasic TMS over the M1 and electric stimulation of the peripheral nerve, induces LTD or long-term potentiation (LTP), depending on the interpair interval (PASLTD at N20-5ms and PASLTP at N20+2ms; heterosynaptic plasticity). Objective: To investigate how the motor cortical excitability is modulated by combining QPS and PAS. Methods: Nine healthy subjects were examined with three intervention protocols; simple QPSLTD, combined PASLTD-QPSLTD, and combined PASLTPQPSLTD applied to the M1. We measured TMS-elicited motor evoked potentials (MEPs) before and after the intervention up to 60 minutes. First, we conducted one-way ANOVA (time) to find the effective time window of each intervention. To compare the effects of different interventions, we then applied one-way ANOVA (intervention) to the MEPs averaged in the defined time window. Results: ANOVA (time) showed a significant main effect (p<0.05). Post-hoc tests revealed significant MEP depression after QPSLTD (10 to 40, and 60 minutes) and PASLTD-QPSLTD (10 to 60 minutes). PASLTP-QPSLTD induced no significant MEP changes. ANOVA (intervention) applied to the mean MEPs in the effective time window showed a significant main effect (p<0.01). PASLTD-QPSLTD depressed MEPs to a greater degree than the other interventions (p<0.05). QPSLTD induced significantly greater depression than PASLTP-QPSLTD (p<0.05).
Introduction: A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve (VNS) has been proposed to enhance extinction memory through the increase of noradrenergic transmission. Method: We conducted two studies (N ¼ 38 & N ¼ 41) to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess fear conditioning and subsequent fear extinction, we assessed US expectancy ratings, fear potentiated startle responses and skin conductance levels. After fear conditioning, participants were randomly assigned to receive tVNS or sham stimulation during the extinction phase (study 1: extinction directly followed acquisition; study 2: extinction followed 24 hours later). Retention of extinction memory was tested 24 hours later. Results: In both studies, tVNS accelerated explicit fear extinction (US expectancy ratings). In study 2, spontaneous recovery for the skin conductance response occurred only in the sham group, but no differences were observed for the other outcomes during retention. Discussion: These findings support the hypothesis that tVNS accelerates declarative extinction learning. The findings are preliminary but consistent with recent studies that indicate that tVNS may be a tool to improve fear extinction. Keywords: transcutaneous vagus nerve stimulation, fear extinction, memory, anxiety
[0240] PAIRED ASSOCIATIVE QUADRIPULSE STIMULATION (PAS-QPS) - A NEW PROTOCOL COMBINING HOMO- AND HETERO-SYNAPTIC PLASTICITY
[0239] THE SPATIAL REPRESENTATION OF TIME IN VISUAL CORTEX nel-Pierre 2, M.M. Murray 2, D. Bueti 1. 1 International G. Fortunato*1, T. Ke School for Advanced Studies (SISSA), Neuroscience Area, Italy; 2 University Hospital of Lausanne, Switzerland Performing a timed movement like dancing, playing a musical instrument or simply walking requires for the brain the integration of both temporal and spatial information. How and where the human brain synergistically links these two types of information remains unclear. Previous studies have shown that primary visual cortex (V1) and extrastriate visual area V5/ MT are both involved in the encoding of temporal information of visual stimuli. However these studies do not clarify how time is encoded in these areas and whether V1 and V5/MT encode time differently. Here we tested the hypothesis that V1 and V5/MT encode time in different spatial coordinates, i.e. head-centred versus eye-centred. To this purpose we asked healthy volunteers to perform a temporal discrimination task of visual stimuli that were presented at varying combinations of retinotopic and head-centred spatiotopic positions. While participants were engaged in this task we interfered with the activity of the right dorsal V1 and the right V5/MT by mean of paired-pulse Transcranial Magnetic Stimulation (ppTMS). The results showed that ppTMS over both areas impaired temporal discrimination thresholds of visual stimuli presented at different
ĂDiscussion: When we combined the LTD-inducing PAS and the LTDinducing QPS, the depressive effects on MEP were additive. In contrast, when we combined the LTP-inducing PAS and LTD-inducing QPS, plasticity effects cancelled out. The combination protocol turned out to be a powerful method to induce MEP changes, which presumably involves physiologically distinct processes of homo- and hetero-synaptic plasticity. Keywords: heterosynaptic plasticity, homosynaptic plasticity, LTD, QPS