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Ketamine infusions after failure to respond to electroconvulsive therapy: a case series report
Abstracts / Brain Stimulation 10 (2017) 346e540
subject's level and provides the basis for precision medicine in neuropsychiatric disorders. Keywords: Mapping, Modulation, TMS/fMRI, high sensitivity MR
491
TO
beneficial effect appears to generalize to unstudied items as well as other cognitive abilities. The results suggest that different montages can produce distinct results depending on the brain area stimulated. Anodal stimulation may be more effective for picture naming when it targets the parietal lobe rather than the frontal lobe. Keywords: Dementia, Anomia, Parietal Lobe, Picture Training
P. Riva-Posse*, G. Galendez Snead, W.M. McDonald. Emory University School of Medicine, USA
[0595] CORTICO-CORTICAL EXCITABILITY IS INFLUENCED BY THE PHASE OF OSCILLATORY ACTIVITY AT THE TIME OF THE STIMULUS
[0591] KETAMINE INFUSIONS AFTER FAILURE TO RESPOND ELECTROCONVULSIVE THERAPY: A CASE SERIES REPORT
Introduction: Treatment resistant depression (TRD) is defined as the failure to remit to a course of at least two adequate antidepressant trials. TRD occurs in approximately 33% of patients with recurrent major depression. Patients with TRD are often referred to electroconvulsive therapy (ECT). Between 20-40% of patients with TRD fail to respond to ECT. There is no clear treatment option for patients that fail ECT. Ketamine has been proposed as a promising treatment for severe depression, but experience with its use is limited. Methods: The Emory TRD Program provides comprehensive evaluations for patients with resistant major depression. Patients who have failed to respond to an adequate course of ECT are the subject of this report. In the past 2 years, 18 patients (9 females, average age: 51 years old) received a series of ketamine infusions after failing to respond to ECT. A series of 6 infusions (0.5 mg/kg over 40 minutes) were done, and maintenance infusions (weekly to biweekly) were offered if response was positive. Patients were evaluated prior to each infusion with Clinical Global Impression Scores of severity and improvement (CGI-S and CGI-I). Results: All patients completed 6 infusions, 16 patients then received maintenance. Baseline CGI-S was 5.3 (markedly to severely ill). Infusions were well tolerated. Response (CGI-I: 1 or 2, very much to much improved) was achieved by 39% after the acute course and 50% in maintenance. A CGIS of 1 or 2 (Normal or borderline mentally ill) was achieved in 28% of patients after 5 infusions and 37.5% of patients in maintenance. Conclusion: Ketamine infusion therapy has promising results in patients with severe TRD that have failed ECT. Keywords: treatment resistant depression, ketamine, electroconvulsive therapy, case series [0592] DEMENTIA PATIENTS HAVE REDUCED ANOMIA FOLLOWING PICTURE NAMING TRANING AND ANODAL TDCS STIMULATION C. Roncero*, E. Service, M. Malus, S. Solomon, A. Thiel, S. Probst, H. Chertkow. McGill University, Canada Introduction: Examine whether transcranial direct current stimulation (tDCS) could help improve picture naming abilities in people living with dementia (Alzheimer’s and frontotemporal). Methods: Utilizing a double-blind cross-over design, twelve participants were trained on picture naming over a series of 10 sessions of 30 minutes of anodal (2 mA) tDCS stimulation to the parietal lobe (P3), frontal lobe (F3) or sham stimulation. Evaluation was carried out before stimulation, on the final stimulation session, two weeks post-stimulation, and two months poststimulation. We evaluated performance on a trained picture naming set, on an equivalent untrained set, and on a set of additional neuropsychological tasks. Results: Participants improved significantly more on the training set after receiving real anodal stimulation (parietal or frontal) compared to when they received sham tDCS. Furthermore, participants who received real stimulation maintained significantly higher naming score at all evaluations, including two months post-stimulation. For untrained items, participants also benefited more from real anodal stimulation than sham stimulation. When parietal stimulation was given, participants demonstrated an improvement that remained significant two months post stimulation, while there was neither an increase nor a decrease when frontal stimulation was given, but a significant decrease two months post-stimulation when sham stimulation was given. Finally, participants showed a small increase for untrained picture naming items and digit span when they received real anodal parietal stimulation, but a decrease when sham stimulation was received. Discussion: The found results suggest tDCS stimulation has promise as a treatment for people with dementia who suffer from anomia, and the
D. Desideri*, P. Belardinelli, C. Zrenner, U. Ziemann. University of Tübingen, Germany Introduction: Single pulse TMS elicits cortical responses that can be observed in the co-registered EEG. These TMS-evoked potentials (TEPs) represent a marker of cortico-cortical excitability, but still little is known about the possible role of the endogenous ongoing oscillations in the stimulated cortical site in the generation of TEPs. Recently it has been shown that the instantaneous phase of the sensorimotor mu-alpha oscillation influences cortico-spinal excitability. In this study, we explore the modulation of cortico-cortical excitability through the interaction between single pulse TMS and the phase of ongoing sensorimotor rhythms. Methods: A real-time custom-made Simulink model has been used to trigger single TMS pulses over the left motor cortex on the basis of the instantaneously estimated phase of the sensorimotor rhythms isolated with a Hjorth spatial filter in the 5 EEG electrodes centered around C3. EEG epochs have been offline sub-selected to match the size of the motor evoked potentials across different phase conditions in order to avoid the possible confounder of the re-afferent feedback. Evoked and induced cortical responses to TMS observed in the EEG have been analysed by means of time-locked average and time-frequency representations based on Morlet wavelets. Results: Different brain rhythms play a role in the generation of TMS evoked responses and in the modulation of cortico-cortical excitability. Discussion: Brain networks communicate by means of oscillations. Different phases of these oscillations represent different excitability states that may play a role in the spatio-temporal evolution of TMS evoked and induced cortical responses . The possibility to consistently deliver single TMS pulses at the same phase of endogenous ongoing brain oscillations and the analysis of cortical responses recorded with EEG represent a powerful way to uncover new aspects of brain dynamics both on a local and network scale. Keywords: TMS, EEG, Cortico-cortical excitability, Oscillations [0596] INTERHEMISPHERIC COMMUNICATION THROUGH NEURONAL COHERENCE REVEALED BY CLOSED-LOOP EEG-DUAL-SITE-TMS M.I. Stefanou*, D. Desideri, P. Belardinelli, C. Zrenner, U. Ziemann. Hertie Institute for Clinical Brain Research, Germany Introduction: Interhemispheric communication (IHC) has been extensively studied using paired-pulse TMS protocols. At different ISIs and stimulus intensities, short-latency interhemispheric inhibition (sIHI) or facilitation (sIHF) are noted, yet, with highly variable responses. Other determinants of inter-trial/inter-individual variability of IHC have not been investigated. In the present study, we examined the dependence of sIHI/sIHF on instantaneous brain-state, i.e., the phase of m-rhythm in the conditioning and test M1. Methods: 12 subjects with m-rhythm (alpha-peak) around C3 and C4 EEG electrodes using Hjorth transformation were studied. EMG from APB and FDI of both hands was acquired. The conditioning M1 was the left M1 and the test M1 was the right M1 at ISIs of 8ms. CS/TS were applied if the m-power in both M1s was above a threshold criterion. We used 4 interleaved conditions based on the phase of m-oscillation from the two M1s: (1) Negative peak (cM1) & negative peak (tM1); (2) Negative peak (cM1) & positive peak (tM1); (3) Positive peak (cM1) & negative peak (tM1); (4) Positive peak (cM1) & positive peak (tM1). 150 trials were obtained for each condition. Results: We successfully performed online estimation of the instantaneous phase of the m-rhythm of the two M1s with precise phase-dependent TMS triggering. Prestimulus alpha phase synchronicity of the two M1s was related with bigger IHC, attenuation of MEPs in the positive-positive condition and increase of the MEPs in the negative-negative condition. A
subject's level and provides the basis for precision medicine in neuropsychiatric disorders. Keywords: Mapping, Modulation, TMS/fMRI, high sensitivity MR
491
TO
beneficial effect appears to generalize to unstudied items as well as other cognitive abilities. The results suggest that different montages can produce distinct results depending on the brain area stimulated. Anodal stimulation may be more effective for picture naming when it targets the parietal lobe rather than the frontal lobe. Keywords: Dementia, Anomia, Parietal Lobe, Picture Training
P. Riva-Posse*, G. Galendez Snead, W.M. McDonald. Emory University School of Medicine, USA
[0595] CORTICO-CORTICAL EXCITABILITY IS INFLUENCED BY THE PHASE OF OSCILLATORY ACTIVITY AT THE TIME OF THE STIMULUS
[0591] KETAMINE INFUSIONS AFTER FAILURE TO RESPOND ELECTROCONVULSIVE THERAPY: A CASE SERIES REPORT
Introduction: Treatment resistant depression (TRD) is defined as the failure to remit to a course of at least two adequate antidepressant trials. TRD occurs in approximately 33% of patients with recurrent major depression. Patients with TRD are often referred to electroconvulsive therapy (ECT). Between 20-40% of patients with TRD fail to respond to ECT. There is no clear treatment option for patients that fail ECT. Ketamine has been proposed as a promising treatment for severe depression, but experience with its use is limited. Methods: The Emory TRD Program provides comprehensive evaluations for patients with resistant major depression. Patients who have failed to respond to an adequate course of ECT are the subject of this report. In the past 2 years, 18 patients (9 females, average age: 51 years old) received a series of ketamine infusions after failing to respond to ECT. A series of 6 infusions (0.5 mg/kg over 40 minutes) were done, and maintenance infusions (weekly to biweekly) were offered if response was positive. Patients were evaluated prior to each infusion with Clinical Global Impression Scores of severity and improvement (CGI-S and CGI-I). Results: All patients completed 6 infusions, 16 patients then received maintenance. Baseline CGI-S was 5.3 (markedly to severely ill). Infusions were well tolerated. Response (CGI-I: 1 or 2, very much to much improved) was achieved by 39% after the acute course and 50% in maintenance. A CGIS of 1 or 2 (Normal or borderline mentally ill) was achieved in 28% of patients after 5 infusions and 37.5% of patients in maintenance. Conclusion: Ketamine infusion therapy has promising results in patients with severe TRD that have failed ECT. Keywords: treatment resistant depression, ketamine, electroconvulsive therapy, case series [0592] DEMENTIA PATIENTS HAVE REDUCED ANOMIA FOLLOWING PICTURE NAMING TRANING AND ANODAL TDCS STIMULATION C. Roncero*, E. Service, M. Malus, S. Solomon, A. Thiel, S. Probst, H. Chertkow. McGill University, Canada Introduction: Examine whether transcranial direct current stimulation (tDCS) could help improve picture naming abilities in people living with dementia (Alzheimer’s and frontotemporal). Methods: Utilizing a double-blind cross-over design, twelve participants were trained on picture naming over a series of 10 sessions of 30 minutes of anodal (2 mA) tDCS stimulation to the parietal lobe (P3), frontal lobe (F3) or sham stimulation. Evaluation was carried out before stimulation, on the final stimulation session, two weeks post-stimulation, and two months poststimulation. We evaluated performance on a trained picture naming set, on an equivalent untrained set, and on a set of additional neuropsychological tasks. Results: Participants improved significantly more on the training set after receiving real anodal stimulation (parietal or frontal) compared to when they received sham tDCS. Furthermore, participants who received real stimulation maintained significantly higher naming score at all evaluations, including two months post-stimulation. For untrained items, participants also benefited more from real anodal stimulation than sham stimulation. When parietal stimulation was given, participants demonstrated an improvement that remained significant two months post stimulation, while there was neither an increase nor a decrease when frontal stimulation was given, but a significant decrease two months post-stimulation when sham stimulation was given. Finally, participants showed a small increase for untrained picture naming items and digit span when they received real anodal parietal stimulation, but a decrease when sham stimulation was received. Discussion: The found results suggest tDCS stimulation has promise as a treatment for people with dementia who suffer from anomia, and the
D. Desideri*, P. Belardinelli, C. Zrenner, U. Ziemann. University of Tübingen, Germany Introduction: Single pulse TMS elicits cortical responses that can be observed in the co-registered EEG. These TMS-evoked potentials (TEPs) represent a marker of cortico-cortical excitability, but still little is known about the possible role of the endogenous ongoing oscillations in the stimulated cortical site in the generation of TEPs. Recently it has been shown that the instantaneous phase of the sensorimotor mu-alpha oscillation influences cortico-spinal excitability. In this study, we explore the modulation of cortico-cortical excitability through the interaction between single pulse TMS and the phase of ongoing sensorimotor rhythms. Methods: A real-time custom-made Simulink model has been used to trigger single TMS pulses over the left motor cortex on the basis of the instantaneously estimated phase of the sensorimotor rhythms isolated with a Hjorth spatial filter in the 5 EEG electrodes centered around C3. EEG epochs have been offline sub-selected to match the size of the motor evoked potentials across different phase conditions in order to avoid the possible confounder of the re-afferent feedback. Evoked and induced cortical responses to TMS observed in the EEG have been analysed by means of time-locked average and time-frequency representations based on Morlet wavelets. Results: Different brain rhythms play a role in the generation of TMS evoked responses and in the modulation of cortico-cortical excitability. Discussion: Brain networks communicate by means of oscillations. Different phases of these oscillations represent different excitability states that may play a role in the spatio-temporal evolution of TMS evoked and induced cortical responses . The possibility to consistently deliver single TMS pulses at the same phase of endogenous ongoing brain oscillations and the analysis of cortical responses recorded with EEG represent a powerful way to uncover new aspects of brain dynamics both on a local and network scale. Keywords: TMS, EEG, Cortico-cortical excitability, Oscillations [0596] INTERHEMISPHERIC COMMUNICATION THROUGH NEURONAL COHERENCE REVEALED BY CLOSED-LOOP EEG-DUAL-SITE-TMS M.I. Stefanou*, D. Desideri, P. Belardinelli, C. Zrenner, U. Ziemann. Hertie Institute for Clinical Brain Research, Germany Introduction: Interhemispheric communication (IHC) has been extensively studied using paired-pulse TMS protocols. At different ISIs and stimulus intensities, short-latency interhemispheric inhibition (sIHI) or facilitation (sIHF) are noted, yet, with highly variable responses. Other determinants of inter-trial/inter-individual variability of IHC have not been investigated. In the present study, we examined the dependence of sIHI/sIHF on instantaneous brain-state, i.e., the phase of m-rhythm in the conditioning and test M1. Methods: 12 subjects with m-rhythm (alpha-peak) around C3 and C4 EEG electrodes using Hjorth transformation were studied. EMG from APB and FDI of both hands was acquired. The conditioning M1 was the left M1 and the test M1 was the right M1 at ISIs of 8ms. CS/TS were applied if the m-power in both M1s was above a threshold criterion. We used 4 interleaved conditions based on the phase of m-oscillation from the two M1s: (1) Negative peak (cM1) & negative peak (tM1); (2) Negative peak (cM1) & positive peak (tM1); (3) Positive peak (cM1) & negative peak (tM1); (4) Positive peak (cM1) & positive peak (tM1). 150 trials were obtained for each condition. Results: We successfully performed online estimation of the instantaneous phase of the m-rhythm of the two M1s with precise phase-dependent TMS triggering. Prestimulus alpha phase synchronicity of the two M1s was related with bigger IHC, attenuation of MEPs in the positive-positive condition and increase of the MEPs in the negative-negative condition. A