- Email: [email protected]
P 235. Focal EEG effects of High Definition tDCS (HD-tDCS) detected by EEG photic driving
e178
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
Medicine, Departments of Neuropsychiatry, Assiut, Egypt, b Assiut University Faculty of Medicine, Assiut, Egypt, c UCL, Institute of Neurology, London, United Kingdom)
Fig. 1. TMS representation of the FDI in human (A) and monkey (B). Blue dots represent stimulation sites, the black dot the center of gravity. Colors indicate average MEP amplitudes from maximum (red; A: 1.85 mV, B: 1.22 mV) to minimum (blue; A: 0.01 mV, B: 0.03 mV).
Results: TMS Mapping sessions took about 80–90 min in each subject with a pulse interval of 8 s. Preparations lasted about 20 min. A closely spaced TMS representation of FDI could be identified in each subject within the precentral gyrus. The shape of the representation area resembled ovals with a mean maximum MEP amplitude of 1.35 mV (SD: 0.52). Mean stereotaxic coordinates of the centers of gravity were ( 36, 12, 67) in MNI152 space. In the animal experiment, the monkey adapted to the setup within 4 weeks. The preparation time for each session was about 10 min. Across all sessions muscle relaxation was present during 64% of the pulses. The pulse interval was 13.4 s. Four repetitions of a complete grid could be recorded in a single session of about 45 min duration. MEPs from contralateral FDI were elicited from a highly defined elliptical area (1 1.5 cm) within the precentral gyrus. Conclusion: Due to the combination of fast high-precision coil positioning and online head tracking, robot-assisted and imageguided TMS is exquisitely suited to perform randomized TMS mappings in the human with acceptable preparation times. In addition, this method allows for precise TMS mapping of the considerably smaller rhesus brain where high-precision coil positioning with a high inter-session reliability is required for multiple session mappings with grid sizes in the millimeter scale.
Fig. 1. doi:10.1016/j.clinph.2013.04.310
P 234. Transcranial direct current stimulation and Alzheimer’s disease—E. Khedr a, N. Foly El Gamal a, N. Abo El-Fetoh a, H. Khalifa a, A. Karim b, J. Rothwell c (a Assiut University Faculty of
Objective: This study was done to compare the effect of anodal, cathodal or sham transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex (DLPFC) on cognitive function in patients with Alzheimer disease (AD). Material and methods: 34 AD patients with mild to moderate disease were randomly classified into three groups. The first group received anodal tDCS and 2nd group received cathodal tDCS and the 3rd group received sham tDCS stimulation over the left DLPFC, daily for 10 days (2 mA for 25 min every weekday for 2 weeks). Minimental State Examination (MMSE) and the verbal and performance scores of the Wechsler Adult Intelligent Scale (WAIS) were assessed before, after the 10 sessions, and then after 1, and 2 months later. Results: There were no significant differences between groups in any of the demographic, clinical data or the rating scales at baseline. A two factor ANOVA with GROUP (anodal, cathodal, sham) and TIME (before, after, 1, 2 months) as main factors showed a significant GROUP TIME interaction for the MMSE (df = 3,2, F = 3.2, p = 0.02) and a borderline significant effect for performance IQ (df = 3,2, F = XX, p = 0.044) but not verbal IQ. Post hoc paired comparisons of the groups showed that both anodal and cathodal TDCS improved MMSE by approx. 3 points versus sham. Only cathodal TDCS improved the performance IQ (by approx. 4 points). Conclusion: These results suggest that 10 daily sessions of either cathodal or anodal tDCS over the DLPFC can produce a sustained improvement in MMSE for at least 2 months in AD. There was a small effect of cathodal TDCS on performance IQ. doi:10.1016/j.clinph.2013.04.311
P 235. Focal EEG effects of High Definition tDCS (HD-tDCS) detected by EEG photic driving—V.V. Lazarev a, T. Tamborino a, M. Bikson b, M.L. Ferreira a, L. deAzevedo a, E.M. Caparelli-Dáquer c (a Fernandes Figueira Inst., FIOCRUZ, Rio de Janeiro, Brazil, b The City College of New York of CUNY, Department of Biomedical Engineering, New York, United Kingdom, c UERJ, Dpt. Ciências Fisiológicas, Rio de Janeiro, Brazil) HD-tDCS using a 4 1-ring configuration has been proposed as an alternative to conventional tDCS, capable to restrict effective current to an area within the ring perimeter. Previously we observed that HD-tDCS stimulation achieves changes in TMS-evoked motor responses comparable to conventional tDCS. In order to investigate focality predicted by computational models, here we used EEG to detect neuronal changes both inside and outside stimulated region. On 15 normal subjects (5 males, 21–57 years), an EEG cap with special electrode holders arranged according to the 4 1-ring configuration was placed with the central electrode holder over central area of the left hemisphere (C3). The peripheral holders were spaced 5 cm radially around the central holder at the corners of a square. Monopolar EEG (linked earlobes reference, eyes closed) was recorded inside stimulation area in the central 4 1 (anode-AnC3), post-central (medial cathode-Ct-C3p), pre-central (between the anode and two anterior cathodes-Int-C3a) positions, outside the stimulation area in the left occipital lead (O1) and at the homologous right hemisphere points (C4a, C4, C4p and O2). EEG recordings were performed during intermittent photic stimulation (IPS) of fixed frequencies 3, 5, 10 and 21 Hz with 30s intervals between stimulation runs as well as during 3 min resting states before (1st) and after (2nd background) IPS sessions. After the initial EEG recording of 9.5– 10 min duration, stimulation was delivered through a battery-driven
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
constant current stimulator connected to a HD-tDCS adaptor device (Soterix Medical Inc., New York, NY). The current was delivered with a ramp-up time of 10s, held at 2 mA for 20 min, and then ramped down over 10 s. EEG was recorded 2–3 min after HD-tDCS. EEG amplitude spectra before and after HD-tDCS were compared for the background states in the 6 standard frequency bands and for the IPS states at all the EEG frequencies corresponding to those of IPS and its harmonics up to 30 Hz. A generalized increase in amplitude spectra after HD-tDCS was observed for the IPS of 3 Hz at the EEG frequencies of 3, 6, 9 and 24 Hz (fundamental frequency and 2nd, 3rd and 8th harmonics), this effect being significantly lower in the stimulation area of the left hemisphere (An-C3, Ct-C3p and Int-C3a) as compared to the homologous leads of the right hemisphere, with lower increase in the An-C3 as compared to the CtC3p at 6 and 24 Hz. No interhemispheric asymmetry was observed between occipital regions (O1 and O2). Similar increase was also observed for the 2nd background state in relation to the same state before HD-tDCS) in An-C3, Int-C3a, C4, and C4a in the theta band, in all the right hemisphere leads and in An-C3 and Ct-C3p in the alpha band with significant right-side prevalence, and in C4, C4a, and C4p in the beta-1 band. The earlier 1st background state after HD-tDCS did not show significant changes. These results are in accordance with HD-tDCS producing focal changes in brain function.
doi:10.1016/j.clinph.2013.04.312
e179
timeand accuracy for discrimination and visual sensitivity (d’) for the detection task. Results: Our interventions revealed hemisphere-specific modulations of frontal oscillatory activity on the visual detection task. More specifically, on the right FEF frequency-specific high-beta TMS bursts enhanced perceptual sensitivity (d’) as compared to sham bursts, whereas no visual performance effects derived from the use of non-frequency-specific patterns. On the left FEF, however, only the non-frequency-specific TMS pattern yielded significant perceptual sensitivity (d’) improvements, whereas no visual performance effects emerged from the use of frequency-specific high-beta bursts. No significant modulations were observed for the discrimination task with any of the TMS patterns employed in the experiment. Conclusions: Our results provide causal evidence in favor of hemisphere-specific frontal contributions to the modulation of visual performance and suggests different but complementary oscillation based mechanisms for the right and the left FEF in such phenomena. Acknowledgements Study funded by FP6 (EU VIth Frame Program) & ANR (Agence National de la Recherche Scientifique) project eraNET-NEURON BEYONDVIS to Dr. A. Valero-Cabré. We thank the IFRAD foundation for providing equipment funds. L. Chanes was supported by a PhD fellowship of the École des Neurosciences de Paris (ENP). doi:10.1016/j.clinph.2013.04.313
P 236. Causal contributions of right and left frontal oscillatory activity to visual performance probed with high-beta rhythmic and arrhythmic patterns of non-invasive stimulation—A. ValeroCabré a,b,c, R. Quentin a, L. Chanes a (a Université Pierre et Marie Curie, CNRS UMR 7225-INSERM UMRS S975, Groupe Centre de Recherche de l’Institut du Cerveau et la Moelle (ICM), Paris, France, b Boston University School of Medicine, Laboratory for Cerebral Dynamics Plasticity & Rehabilitation, Boston, United States, c Open University of Catalonia (UOC), Cognitive Neuroscience and Information Technology Research Program, Barcelona, Spain) Introduction: Despite growing evidence of the fundamental role played by cerebral oscillations in neural signaling and processing, the region-and hemisphere-specific contributions of frontal brain oscillatory activity to human visual cognition remains to be causally explored. Objectives: In the current study, we aimed to explore the effects of 30 Hz oscillation patterns induced by rhythmic rTMS on the right and left Frontal Eye Fields, a region involved in attentional spatial orienting, and analyzed the impact of such intervention on visual discrimination and detection performance. Material and methods: In two separate populations of subjects, we applied 4 pulse real or sham TMS bursts either to the left or the right Frontal Eye Fields (FEF) to manipulate local oscillatory activity and study the impact of such on the visual detection and categorization of low-contrast near-threshold targets. During the task subjects were requested to fixate on a central cross and following the appearance of a Gabor in a peripheral location (right/left) and perform two consecutive tasks in this order: First a force-choice visual discrimination to indicate the orientation of the gratings within the stimulus (right/left); Second, a visual detection task to report if they had seen the target and in case they did, where it did appear (yes/no and right/ left). In separate experimental blocks, in order to control for the effects of frequency, we compared the impact of frequency specific rTMS patterns (rhythmic) at high-beta (30 Hz) frequency to non-frequency-specific (a-rhythmic) rTMS patterns, matched in duration and number of pulses on correlates of visual performance: reaction
Poster Session II Therapeutic Applications II P 237. Repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury-a pilot RCT—M. Lesniak, K. Polanowska, J. Seniów (Institute of Psychiatry & Neurology, 2nd Department of Neurology, Warsaw, Poland) Question: Does repeated anodal transcranial direct current stimulation (A-tDCS) of the left dorso-lateral prefrontal cortex (DLPFC) enhance cognitive rehabilitation effects on memory and attention in patients with traumatic brain injury (TBI). Methods: Twenty-three adult patients, 4–92 months post severe TBI, were randomly allocated to two groups. The experimental group received A-tDCS (10 min; 1 mA; in the DLPFC), followed by 1-h cognitive training, daily for 15 days. Controls received AtDCS for 25 s (sham condition) with the same rehabilitation programme. Effects of the treatment were assessed using a battery of memory and attention tests (Rey’s Auditory Verbal Learning Test, Paced Auditory Serial Addition Test, Cambridge Neuropsychological Test Automated Battery), which included visual and auditory modalities. Additionally, European Brain Injury Questionaire was used to assess functional gains in daily activities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and four months later. Results: Tests scores in both groups were similar at three weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in six out of eight cognitive outcome measures, but they were not significantly different from controls. At follow-up, experimental group’s effect sizes were higher in five outcome measures. However, differences remained insignificant. No serious adverse effects were observed during the programme. Conclusion: In contrast to previous studies, our study did not provide sufficiently strong evidence to support the efficacy of repeated A-tDCS over the left DLPFC for enhancing rehabilitation of memory
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
Medicine, Departments of Neuropsychiatry, Assiut, Egypt, b Assiut University Faculty of Medicine, Assiut, Egypt, c UCL, Institute of Neurology, London, United Kingdom)
Fig. 1. TMS representation of the FDI in human (A) and monkey (B). Blue dots represent stimulation sites, the black dot the center of gravity. Colors indicate average MEP amplitudes from maximum (red; A: 1.85 mV, B: 1.22 mV) to minimum (blue; A: 0.01 mV, B: 0.03 mV).
Results: TMS Mapping sessions took about 80–90 min in each subject with a pulse interval of 8 s. Preparations lasted about 20 min. A closely spaced TMS representation of FDI could be identified in each subject within the precentral gyrus. The shape of the representation area resembled ovals with a mean maximum MEP amplitude of 1.35 mV (SD: 0.52). Mean stereotaxic coordinates of the centers of gravity were ( 36, 12, 67) in MNI152 space. In the animal experiment, the monkey adapted to the setup within 4 weeks. The preparation time for each session was about 10 min. Across all sessions muscle relaxation was present during 64% of the pulses. The pulse interval was 13.4 s. Four repetitions of a complete grid could be recorded in a single session of about 45 min duration. MEPs from contralateral FDI were elicited from a highly defined elliptical area (1 1.5 cm) within the precentral gyrus. Conclusion: Due to the combination of fast high-precision coil positioning and online head tracking, robot-assisted and imageguided TMS is exquisitely suited to perform randomized TMS mappings in the human with acceptable preparation times. In addition, this method allows for precise TMS mapping of the considerably smaller rhesus brain where high-precision coil positioning with a high inter-session reliability is required for multiple session mappings with grid sizes in the millimeter scale.
Fig. 1. doi:10.1016/j.clinph.2013.04.310
P 234. Transcranial direct current stimulation and Alzheimer’s disease—E. Khedr a, N. Foly El Gamal a, N. Abo El-Fetoh a, H. Khalifa a, A. Karim b, J. Rothwell c (a Assiut University Faculty of
Objective: This study was done to compare the effect of anodal, cathodal or sham transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex (DLPFC) on cognitive function in patients with Alzheimer disease (AD). Material and methods: 34 AD patients with mild to moderate disease were randomly classified into three groups. The first group received anodal tDCS and 2nd group received cathodal tDCS and the 3rd group received sham tDCS stimulation over the left DLPFC, daily for 10 days (2 mA for 25 min every weekday for 2 weeks). Minimental State Examination (MMSE) and the verbal and performance scores of the Wechsler Adult Intelligent Scale (WAIS) were assessed before, after the 10 sessions, and then after 1, and 2 months later. Results: There were no significant differences between groups in any of the demographic, clinical data or the rating scales at baseline. A two factor ANOVA with GROUP (anodal, cathodal, sham) and TIME (before, after, 1, 2 months) as main factors showed a significant GROUP TIME interaction for the MMSE (df = 3,2, F = 3.2, p = 0.02) and a borderline significant effect for performance IQ (df = 3,2, F = XX, p = 0.044) but not verbal IQ. Post hoc paired comparisons of the groups showed that both anodal and cathodal TDCS improved MMSE by approx. 3 points versus sham. Only cathodal TDCS improved the performance IQ (by approx. 4 points). Conclusion: These results suggest that 10 daily sessions of either cathodal or anodal tDCS over the DLPFC can produce a sustained improvement in MMSE for at least 2 months in AD. There was a small effect of cathodal TDCS on performance IQ. doi:10.1016/j.clinph.2013.04.311
P 235. Focal EEG effects of High Definition tDCS (HD-tDCS) detected by EEG photic driving—V.V. Lazarev a, T. Tamborino a, M. Bikson b, M.L. Ferreira a, L. deAzevedo a, E.M. Caparelli-Dáquer c (a Fernandes Figueira Inst., FIOCRUZ, Rio de Janeiro, Brazil, b The City College of New York of CUNY, Department of Biomedical Engineering, New York, United Kingdom, c UERJ, Dpt. Ciências Fisiológicas, Rio de Janeiro, Brazil) HD-tDCS using a 4 1-ring configuration has been proposed as an alternative to conventional tDCS, capable to restrict effective current to an area within the ring perimeter. Previously we observed that HD-tDCS stimulation achieves changes in TMS-evoked motor responses comparable to conventional tDCS. In order to investigate focality predicted by computational models, here we used EEG to detect neuronal changes both inside and outside stimulated region. On 15 normal subjects (5 males, 21–57 years), an EEG cap with special electrode holders arranged according to the 4 1-ring configuration was placed with the central electrode holder over central area of the left hemisphere (C3). The peripheral holders were spaced 5 cm radially around the central holder at the corners of a square. Monopolar EEG (linked earlobes reference, eyes closed) was recorded inside stimulation area in the central 4 1 (anode-AnC3), post-central (medial cathode-Ct-C3p), pre-central (between the anode and two anterior cathodes-Int-C3a) positions, outside the stimulation area in the left occipital lead (O1) and at the homologous right hemisphere points (C4a, C4, C4p and O2). EEG recordings were performed during intermittent photic stimulation (IPS) of fixed frequencies 3, 5, 10 and 21 Hz with 30s intervals between stimulation runs as well as during 3 min resting states before (1st) and after (2nd background) IPS sessions. After the initial EEG recording of 9.5– 10 min duration, stimulation was delivered through a battery-driven
Society Proceedings / Clinical Neurophysiology 124 (2013) e39–e187
constant current stimulator connected to a HD-tDCS adaptor device (Soterix Medical Inc., New York, NY). The current was delivered with a ramp-up time of 10s, held at 2 mA for 20 min, and then ramped down over 10 s. EEG was recorded 2–3 min after HD-tDCS. EEG amplitude spectra before and after HD-tDCS were compared for the background states in the 6 standard frequency bands and for the IPS states at all the EEG frequencies corresponding to those of IPS and its harmonics up to 30 Hz. A generalized increase in amplitude spectra after HD-tDCS was observed for the IPS of 3 Hz at the EEG frequencies of 3, 6, 9 and 24 Hz (fundamental frequency and 2nd, 3rd and 8th harmonics), this effect being significantly lower in the stimulation area of the left hemisphere (An-C3, Ct-C3p and Int-C3a) as compared to the homologous leads of the right hemisphere, with lower increase in the An-C3 as compared to the CtC3p at 6 and 24 Hz. No interhemispheric asymmetry was observed between occipital regions (O1 and O2). Similar increase was also observed for the 2nd background state in relation to the same state before HD-tDCS) in An-C3, Int-C3a, C4, and C4a in the theta band, in all the right hemisphere leads and in An-C3 and Ct-C3p in the alpha band with significant right-side prevalence, and in C4, C4a, and C4p in the beta-1 band. The earlier 1st background state after HD-tDCS did not show significant changes. These results are in accordance with HD-tDCS producing focal changes in brain function.
doi:10.1016/j.clinph.2013.04.312
e179
timeand accuracy for discrimination and visual sensitivity (d’) for the detection task. Results: Our interventions revealed hemisphere-specific modulations of frontal oscillatory activity on the visual detection task. More specifically, on the right FEF frequency-specific high-beta TMS bursts enhanced perceptual sensitivity (d’) as compared to sham bursts, whereas no visual performance effects derived from the use of non-frequency-specific patterns. On the left FEF, however, only the non-frequency-specific TMS pattern yielded significant perceptual sensitivity (d’) improvements, whereas no visual performance effects emerged from the use of frequency-specific high-beta bursts. No significant modulations were observed for the discrimination task with any of the TMS patterns employed in the experiment. Conclusions: Our results provide causal evidence in favor of hemisphere-specific frontal contributions to the modulation of visual performance and suggests different but complementary oscillation based mechanisms for the right and the left FEF in such phenomena. Acknowledgements Study funded by FP6 (EU VIth Frame Program) & ANR (Agence National de la Recherche Scientifique) project eraNET-NEURON BEYONDVIS to Dr. A. Valero-Cabré. We thank the IFRAD foundation for providing equipment funds. L. Chanes was supported by a PhD fellowship of the École des Neurosciences de Paris (ENP). doi:10.1016/j.clinph.2013.04.313
P 236. Causal contributions of right and left frontal oscillatory activity to visual performance probed with high-beta rhythmic and arrhythmic patterns of non-invasive stimulation—A. ValeroCabré a,b,c, R. Quentin a, L. Chanes a (a Université Pierre et Marie Curie, CNRS UMR 7225-INSERM UMRS S975, Groupe Centre de Recherche de l’Institut du Cerveau et la Moelle (ICM), Paris, France, b Boston University School of Medicine, Laboratory for Cerebral Dynamics Plasticity & Rehabilitation, Boston, United States, c Open University of Catalonia (UOC), Cognitive Neuroscience and Information Technology Research Program, Barcelona, Spain) Introduction: Despite growing evidence of the fundamental role played by cerebral oscillations in neural signaling and processing, the region-and hemisphere-specific contributions of frontal brain oscillatory activity to human visual cognition remains to be causally explored. Objectives: In the current study, we aimed to explore the effects of 30 Hz oscillation patterns induced by rhythmic rTMS on the right and left Frontal Eye Fields, a region involved in attentional spatial orienting, and analyzed the impact of such intervention on visual discrimination and detection performance. Material and methods: In two separate populations of subjects, we applied 4 pulse real or sham TMS bursts either to the left or the right Frontal Eye Fields (FEF) to manipulate local oscillatory activity and study the impact of such on the visual detection and categorization of low-contrast near-threshold targets. During the task subjects were requested to fixate on a central cross and following the appearance of a Gabor in a peripheral location (right/left) and perform two consecutive tasks in this order: First a force-choice visual discrimination to indicate the orientation of the gratings within the stimulus (right/left); Second, a visual detection task to report if they had seen the target and in case they did, where it did appear (yes/no and right/ left). In separate experimental blocks, in order to control for the effects of frequency, we compared the impact of frequency specific rTMS patterns (rhythmic) at high-beta (30 Hz) frequency to non-frequency-specific (a-rhythmic) rTMS patterns, matched in duration and number of pulses on correlates of visual performance: reaction
Poster Session II Therapeutic Applications II P 237. Repeated anodal tDCS coupled with cognitive training for patients with severe traumatic brain injury-a pilot RCT—M. Lesniak, K. Polanowska, J. Seniów (Institute of Psychiatry & Neurology, 2nd Department of Neurology, Warsaw, Poland) Question: Does repeated anodal transcranial direct current stimulation (A-tDCS) of the left dorso-lateral prefrontal cortex (DLPFC) enhance cognitive rehabilitation effects on memory and attention in patients with traumatic brain injury (TBI). Methods: Twenty-three adult patients, 4–92 months post severe TBI, were randomly allocated to two groups. The experimental group received A-tDCS (10 min; 1 mA; in the DLPFC), followed by 1-h cognitive training, daily for 15 days. Controls received AtDCS for 25 s (sham condition) with the same rehabilitation programme. Effects of the treatment were assessed using a battery of memory and attention tests (Rey’s Auditory Verbal Learning Test, Paced Auditory Serial Addition Test, Cambridge Neuropsychological Test Automated Battery), which included visual and auditory modalities. Additionally, European Brain Injury Questionaire was used to assess functional gains in daily activities. Participants were tested twice before beginning rehabilitation (to control for spontaneous recovery), after rehabilitation completion, and four months later. Results: Tests scores in both groups were similar at three weeks before and immediately before treatment. After treatment, the experimental group exhibited larger effect sizes in six out of eight cognitive outcome measures, but they were not significantly different from controls. At follow-up, experimental group’s effect sizes were higher in five outcome measures. However, differences remained insignificant. No serious adverse effects were observed during the programme. Conclusion: In contrast to previous studies, our study did not provide sufficiently strong evidence to support the efficacy of repeated A-tDCS over the left DLPFC for enhancing rehabilitation of memory