- Email: [email protected]
Shed light on the black box: Using MEG to recover brain activity during tACS
Abstracts / Brain Stimulation 8 (2015) 378e394
the subthalamic nucleus (STN) of 11 patients with Parkinson’s disease and in the nucleus ventralis intermedius (Vim) of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model (COMSOL) was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. Results: All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P ¼ 0.003) and wider than the third best direction (P ¼ 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P ¼ 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67mA (0.3e1.0 mA) and was 43% lower than in omnidirectional stimulation (P ¼ 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm3 in omnidirectional mode, compared with 4.2 mm3 when only one electrode was used. Conclusion: Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the STN as well as in Vim significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.
381
This study demonstrated functional connectivity, which was validated with structural imaging. The combination of TMS-fMRI is a promising tool to investigate connectivity deficits in neuro-psychiatric disorders.
231 Brain plasticity related piano training in youths with neurodevelopmental disorders Renée Lampe , Ana Alves-Pinto , Tobias Blumenstein , Varvara Turova Clinic ‘rechts der Isar’, Technical University of Munich *E-mail: [email protected]. Impaired hand motor skills occur frequently in patients with neurodevelopmental disorders, limiting the performance of daily activities. Improvement of hand motor functions is therefore central in the therapy plan of these patients and in the amelioration of their quality of life. Ten patients with neurodevelopmental disorders, aged between eight and sixteen years, received intensive motor training through piano lessons for one and half years. Another group of six patients received no instrument classes. Potential neuroplasticity induced by the training was assessed by performing functional magnetic resonance imaging before and after the training in both groups. The heterogeneity that characterizes this clinical population, in terms of the extension of brain damages causing the deficits and in terms of the symptomatology, was also observed in the range of changes recorded. Nevertheless, an increase in connectivity between the primary motor cortex contralateral to the dominant hand and the ipsilateral cerebellum was registered and suggests a potential beneficial effect of the piano training. The enjoyment and engagement expressed by the youths during the training supports further the musical instrument training as a promising method in the motor and personal development of these patients.
230 Functional connectivity along the arcuate fasciculus investigated with concurrent TMS-fMRI A.D. de Weijer a,b, I.E.C. Sommer a, S.F.W. Neggers a a Department of Psychiatry, University Medical Centre, Utrecht, The Netherlands b FMRIB Centre, University of Oxford, United Kingdom The application of TMS during the acquisition of functional MRI allows to investigate functional connectivity and to make causal inferences. This study aims to stimulate a temporoparietal region with TMS and to measure the evoked activation pattern with fMRI. Subsequently, the TMS induced activation pattern is related to a reconstruction of the white matter tract that connects the frontal, temporal and parietal region. The combination of these modalities provides information regarding both functional and structural connectivity, and a measurement for tract integrity, which can be used to study a wider range of disorders. Based on the anatomical T1 scan, a site on the left temporoparietal region was defined as target site for TMS. At this cortical region TMS was applied in a 3T MRI scanner, while this TMS induced activation was measured with fMRI. In addition Diffusion Tensor Imaging (DTI) was used to reconstruct the arcuate fasciculus. TMS at the temporoparietal region induced activation in cortical regions such as the ipsilateral inferior frontal gyrus, bilateral supra marginal gyrus, and also contralateral to the stimulation site. A DTI reconstruction of the arcuate fasciculus revealed that the activation pattern in the left hemisphere was located near the endpoints of the arcuate fasciculus.
232 Shed light on the black box: Using MEG to recover brain activity during tACS T. Neuling a, P. Ruhnau b, M. Fuscà b, G. Demarchi b, C.S. Herrmann a,c, N. Weisz b a Experimental Psychology Lab, Center for Excellence ‘‘Hearing4all,’’ European Medical School, University of Oldenburg, Germany b Center for Mind/Brain Sciences, University of Trento, Italy c Research Center Neurosensory Science, University of Oldenburg, Germany Aberrations in the normal functioning of brain oscillations have been linked to cognitive deficits and symptoms of psychiatric diseases, highlighting the need to illustrate their causal role in behavior. An increasingly popular technique to do this is via noninvasive brain stimulation techniques, which ’entrain’ brain rhythms at natural frequencies. One especially suitable technique to modulate brain oscillations is transcranial alternating current stimulation (tACS), whereby weak currents imitating brain oscillations are delivered to the brain. Recent studies have demonstrated robust effects on oscillatory activity by comparing pre- and posttACS periods; however, one main disadvantage is the inability to record and analyze brain activity during stimulation due to the induced artifact. By combining tACS with magnetoencephalography (MEG), we demonstrate that brain oscillations can be reconstructed at the tACS frequency. Although a recent study demonstrated the recovery of oscillatory activity inside the brain during transcranial direct current stimulation (tDCS), it remained to be determined if, due to the
382
Abstracts / Brain Stimulation 8 (2015) 378e394
high synchrony of the brain signal and the stimulation artifact, these signals are separable enough to uncover subtle tACS-induced brain modulations. Using interventions that lead to well-established and robust modulations of alpha power (eyes open vs. closed and stimulus induced alpha power decrease), we demonstrate for the first time that using MEG in conjunction with a spatial filtering technique can successfully disentangle oscillatory brain activity from the highly correlated tACS signal. These techniques provide new opportunities for studying brain activity during ongoing tACS, which will undoubtedly have farreaching implications for both the cognitive and clinical neurosciences.
233 Intra and interhemispheric modulation of motor and somatosensory cortices using cTBS: a TMS/EEG study Gan Huang , André Mouraux Institute of Neuroscience (IONS), Université catholique de Louvain (UCL) Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique widely used to probe the function of a given brain structure. It also has promising therapeutic applications for the treatment of various neuropsychiatric disorders. However, the after-effects of rTMS are highly variable across individuals. Recently, Hamada et al. (2013) found that the effect of continuous theta burst stimulation (cTBS) on M1 could be predicted by the latency of the motor-evoked potentials (MEPs) recorded before applying cTBS. This suggests that inter-individual variability of the effects of rTMS could be driven by differences in the interneuronal networks preferentially activated by TMS. Methods: We investigated the effect of cTBS delivered over M1 on the ipsilateral and contralateral M1 and primary somatosensory cortex (S1) using motor-evoked potentials (MEPs), somatosensoryevoked brain potentials (SEP) and TMS-evoked brain potentials (TEP) recorded from both hemispheres before and after cTBS. Results: Our results confirm that the variable effect of cTBS can be predicted by the latency of the MEPs recorded before applying cTBS. Short MEP latencies were associated with an enhancement of the MEPs elicited by stimulation of the ipsilateral M1 whereas late MEP latencies were associated with a reduction of MEP amplitude. In contrast, there was a positive correlation between MEP latency and the change in the amplitude of the MEPs elicited by stimulation of the contralateral hemisphere. A similar relationship was observed between MEP latency and the effect of cTBS on the magnitude of the N100 wave of TEPs. Finally, there was a group-level effect of cTBS on the magnitude of the N20 and P100 waves of SEPs, which, after cTBS, were decreased over the ipsilateral hemisphere and increased over the contralateral hemisphere. Discussion: The reverse relationship between MEP latency and the effects of cTBS on the ipsilateral and contralateral hemisphere is compatible with interhemispheric inhibitory interactions.
234 Boosting recovery of vision loss in post-acute stroke with tDCS e A pilot Study R. Alber a,*, H. Moser a, B.A. Sabel b, Gall C b a Neurologisches Therapiezentrum Gmundnerberg, Altmünster, Austria b Medical Faculty, Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg, Germany *E-mail: [email protected]. Introduction: Posterior cerebral artery (PCA) stroke usually results in visual field defects varying in size and extent of the blind field. Vision restoration training (VRT) may reduce the visual field
impairment. Combined application of anodal transcranial direct current stimulation (tDCS) over visual cortex together with VRT indicates that tDCS may accelerate VRT-effects in the post-acute stage. We investigated safety, applicability and efficacy in 7 postacute PCA stroke patients and compared their visual field changes to 7 control subject who were matched with respect to lesion-age and defect-size and underwent standard rehabilitation. Methods: Fourteen patients with homonymous field defects after PCA stroke were included in this pilot study. Seven subjects were treated with up to 10 tDCS-sessions (2mA, 15-20 minutes, cathode: Cz, anode: O1/O2) combined with VRT (Anops: LinguAdapt). Data of safety monitoring as well as a survey of side effects was collected. Perimetric detection thresholds (Oculus, Twinfield) after tDCS combined with VRT were compared to baseline to investigate training effects. Control subjects were retrospectively picked out of a data source of patients who underwent a standard rehabilitation program consisting of compensatory eye movement training . Results: Referring to the safety monitoring no negative side effects apart from skin itching beneath the electrodes were reported. Significant improvement of detection accuracy within impaired visual fields was observed in all 14 subjects. However, there was a stronger improvement in patients who received combined VRT and tDCS (36.93% 36.65) compared to controls (10.81% 9.48) Discussion: Concerning this pilot study, the application of tDCS combined with VRT in sub-acute stroke is safe and easily applicable in clinical routine. Anodal tDCS might facilitate rehabilitation of visual field loss, although the tDCS-effect itself can not be sufficiently estimated here due to limitations of the study design. Further studies are needed to compare real-tDCS vs. sham-tDCS in neurovisual rehabilitation.
235 Calculation of the induced electric field of a dedicated transcranial magnetic stimulation coil for the rat A. Miranda , J. Verhaeghe , S. Servaes , J. Parthoens , S. Staelens Molecular Imaging Center Antwerp, University of Antwerp Introduction: Recently our group, in collaboration with Magventure, Denmark, developed a dedicated 40 mm outer diameter circular rat transcranial magnetic stimulation (TMS) coil consisting of two bended layers with 12 windings in each layer operated at a current of 6960 A with a frequency of 3546 Hz. Here we calculated the induced electric field generated by the coil when placed 2 mm above a 15 mm radius tissue-equivalent water sphere mimicking the head of a rat. Methods: Calculations were performed using the finite element simulation software COMSOL multiphysics (4.3 b), using the multiturn coil definition of the magnetic fields physics. The maximum electric field at several depths from the surface were calculated as well as the half power region (HPR), surface area in which jEjjEjmax*0.707. Also the first time derivative of the magnetic field was calculated and measured (measurements provided by the manufacturer). Results: The calculated maximum electric field at the surface of the spherical rat head model was w260 V/m with the amplitude decaying with the depth (figure 1). However, at a depth of 7.5 mm from the sphere surface the maximum induced electric field was still more than 100 V/m. The HPR was located in 12.5 % of the surface area (figure 2). Further, the calculated shape and magnitude of the derivative of the magnetic field were in very close agreement with the experimentally measured field (scaling factor 0.988). Conclusion: The distribution of the induced electric field and the derivative of the magnetic field for the dedicated TMS coil design were calculated. The field exceeded 100 V/m at depths up to 7.5 mm from the surface.
the subthalamic nucleus (STN) of 11 patients with Parkinson’s disease and in the nucleus ventralis intermedius (Vim) of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model (COMSOL) was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. Results: All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P ¼ 0.003) and wider than the third best direction (P ¼ 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P ¼ 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67mA (0.3e1.0 mA) and was 43% lower than in omnidirectional stimulation (P ¼ 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm3 in omnidirectional mode, compared with 4.2 mm3 when only one electrode was used. Conclusion: Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the STN as well as in Vim significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.
381
This study demonstrated functional connectivity, which was validated with structural imaging. The combination of TMS-fMRI is a promising tool to investigate connectivity deficits in neuro-psychiatric disorders.
231 Brain plasticity related piano training in youths with neurodevelopmental disorders Renée Lampe , Ana Alves-Pinto , Tobias Blumenstein , Varvara Turova Clinic ‘rechts der Isar’, Technical University of Munich *E-mail: [email protected]. Impaired hand motor skills occur frequently in patients with neurodevelopmental disorders, limiting the performance of daily activities. Improvement of hand motor functions is therefore central in the therapy plan of these patients and in the amelioration of their quality of life. Ten patients with neurodevelopmental disorders, aged between eight and sixteen years, received intensive motor training through piano lessons for one and half years. Another group of six patients received no instrument classes. Potential neuroplasticity induced by the training was assessed by performing functional magnetic resonance imaging before and after the training in both groups. The heterogeneity that characterizes this clinical population, in terms of the extension of brain damages causing the deficits and in terms of the symptomatology, was also observed in the range of changes recorded. Nevertheless, an increase in connectivity between the primary motor cortex contralateral to the dominant hand and the ipsilateral cerebellum was registered and suggests a potential beneficial effect of the piano training. The enjoyment and engagement expressed by the youths during the training supports further the musical instrument training as a promising method in the motor and personal development of these patients.
230 Functional connectivity along the arcuate fasciculus investigated with concurrent TMS-fMRI A.D. de Weijer a,b, I.E.C. Sommer a, S.F.W. Neggers a a Department of Psychiatry, University Medical Centre, Utrecht, The Netherlands b FMRIB Centre, University of Oxford, United Kingdom The application of TMS during the acquisition of functional MRI allows to investigate functional connectivity and to make causal inferences. This study aims to stimulate a temporoparietal region with TMS and to measure the evoked activation pattern with fMRI. Subsequently, the TMS induced activation pattern is related to a reconstruction of the white matter tract that connects the frontal, temporal and parietal region. The combination of these modalities provides information regarding both functional and structural connectivity, and a measurement for tract integrity, which can be used to study a wider range of disorders. Based on the anatomical T1 scan, a site on the left temporoparietal region was defined as target site for TMS. At this cortical region TMS was applied in a 3T MRI scanner, while this TMS induced activation was measured with fMRI. In addition Diffusion Tensor Imaging (DTI) was used to reconstruct the arcuate fasciculus. TMS at the temporoparietal region induced activation in cortical regions such as the ipsilateral inferior frontal gyrus, bilateral supra marginal gyrus, and also contralateral to the stimulation site. A DTI reconstruction of the arcuate fasciculus revealed that the activation pattern in the left hemisphere was located near the endpoints of the arcuate fasciculus.
232 Shed light on the black box: Using MEG to recover brain activity during tACS T. Neuling a, P. Ruhnau b, M. Fuscà b, G. Demarchi b, C.S. Herrmann a,c, N. Weisz b a Experimental Psychology Lab, Center for Excellence ‘‘Hearing4all,’’ European Medical School, University of Oldenburg, Germany b Center for Mind/Brain Sciences, University of Trento, Italy c Research Center Neurosensory Science, University of Oldenburg, Germany Aberrations in the normal functioning of brain oscillations have been linked to cognitive deficits and symptoms of psychiatric diseases, highlighting the need to illustrate their causal role in behavior. An increasingly popular technique to do this is via noninvasive brain stimulation techniques, which ’entrain’ brain rhythms at natural frequencies. One especially suitable technique to modulate brain oscillations is transcranial alternating current stimulation (tACS), whereby weak currents imitating brain oscillations are delivered to the brain. Recent studies have demonstrated robust effects on oscillatory activity by comparing pre- and posttACS periods; however, one main disadvantage is the inability to record and analyze brain activity during stimulation due to the induced artifact. By combining tACS with magnetoencephalography (MEG), we demonstrate that brain oscillations can be reconstructed at the tACS frequency. Although a recent study demonstrated the recovery of oscillatory activity inside the brain during transcranial direct current stimulation (tDCS), it remained to be determined if, due to the
382
Abstracts / Brain Stimulation 8 (2015) 378e394
high synchrony of the brain signal and the stimulation artifact, these signals are separable enough to uncover subtle tACS-induced brain modulations. Using interventions that lead to well-established and robust modulations of alpha power (eyes open vs. closed and stimulus induced alpha power decrease), we demonstrate for the first time that using MEG in conjunction with a spatial filtering technique can successfully disentangle oscillatory brain activity from the highly correlated tACS signal. These techniques provide new opportunities for studying brain activity during ongoing tACS, which will undoubtedly have farreaching implications for both the cognitive and clinical neurosciences.
233 Intra and interhemispheric modulation of motor and somatosensory cortices using cTBS: a TMS/EEG study Gan Huang , André Mouraux Institute of Neuroscience (IONS), Université catholique de Louvain (UCL) Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique widely used to probe the function of a given brain structure. It also has promising therapeutic applications for the treatment of various neuropsychiatric disorders. However, the after-effects of rTMS are highly variable across individuals. Recently, Hamada et al. (2013) found that the effect of continuous theta burst stimulation (cTBS) on M1 could be predicted by the latency of the motor-evoked potentials (MEPs) recorded before applying cTBS. This suggests that inter-individual variability of the effects of rTMS could be driven by differences in the interneuronal networks preferentially activated by TMS. Methods: We investigated the effect of cTBS delivered over M1 on the ipsilateral and contralateral M1 and primary somatosensory cortex (S1) using motor-evoked potentials (MEPs), somatosensoryevoked brain potentials (SEP) and TMS-evoked brain potentials (TEP) recorded from both hemispheres before and after cTBS. Results: Our results confirm that the variable effect of cTBS can be predicted by the latency of the MEPs recorded before applying cTBS. Short MEP latencies were associated with an enhancement of the MEPs elicited by stimulation of the ipsilateral M1 whereas late MEP latencies were associated with a reduction of MEP amplitude. In contrast, there was a positive correlation between MEP latency and the change in the amplitude of the MEPs elicited by stimulation of the contralateral hemisphere. A similar relationship was observed between MEP latency and the effect of cTBS on the magnitude of the N100 wave of TEPs. Finally, there was a group-level effect of cTBS on the magnitude of the N20 and P100 waves of SEPs, which, after cTBS, were decreased over the ipsilateral hemisphere and increased over the contralateral hemisphere. Discussion: The reverse relationship between MEP latency and the effects of cTBS on the ipsilateral and contralateral hemisphere is compatible with interhemispheric inhibitory interactions.
234 Boosting recovery of vision loss in post-acute stroke with tDCS e A pilot Study R. Alber a,*, H. Moser a, B.A. Sabel b, Gall C b a Neurologisches Therapiezentrum Gmundnerberg, Altmünster, Austria b Medical Faculty, Institute of Medical Psychology, Otto-von-Guericke University, Magdeburg, Germany *E-mail: [email protected]. Introduction: Posterior cerebral artery (PCA) stroke usually results in visual field defects varying in size and extent of the blind field. Vision restoration training (VRT) may reduce the visual field
impairment. Combined application of anodal transcranial direct current stimulation (tDCS) over visual cortex together with VRT indicates that tDCS may accelerate VRT-effects in the post-acute stage. We investigated safety, applicability and efficacy in 7 postacute PCA stroke patients and compared their visual field changes to 7 control subject who were matched with respect to lesion-age and defect-size and underwent standard rehabilitation. Methods: Fourteen patients with homonymous field defects after PCA stroke were included in this pilot study. Seven subjects were treated with up to 10 tDCS-sessions (2mA, 15-20 minutes, cathode: Cz, anode: O1/O2) combined with VRT (Anops: LinguAdapt). Data of safety monitoring as well as a survey of side effects was collected. Perimetric detection thresholds (Oculus, Twinfield) after tDCS combined with VRT were compared to baseline to investigate training effects. Control subjects were retrospectively picked out of a data source of patients who underwent a standard rehabilitation program consisting of compensatory eye movement training . Results: Referring to the safety monitoring no negative side effects apart from skin itching beneath the electrodes were reported. Significant improvement of detection accuracy within impaired visual fields was observed in all 14 subjects. However, there was a stronger improvement in patients who received combined VRT and tDCS (36.93% 36.65) compared to controls (10.81% 9.48) Discussion: Concerning this pilot study, the application of tDCS combined with VRT in sub-acute stroke is safe and easily applicable in clinical routine. Anodal tDCS might facilitate rehabilitation of visual field loss, although the tDCS-effect itself can not be sufficiently estimated here due to limitations of the study design. Further studies are needed to compare real-tDCS vs. sham-tDCS in neurovisual rehabilitation.
235 Calculation of the induced electric field of a dedicated transcranial magnetic stimulation coil for the rat A. Miranda , J. Verhaeghe , S. Servaes , J. Parthoens , S. Staelens Molecular Imaging Center Antwerp, University of Antwerp Introduction: Recently our group, in collaboration with Magventure, Denmark, developed a dedicated 40 mm outer diameter circular rat transcranial magnetic stimulation (TMS) coil consisting of two bended layers with 12 windings in each layer operated at a current of 6960 A with a frequency of 3546 Hz. Here we calculated the induced electric field generated by the coil when placed 2 mm above a 15 mm radius tissue-equivalent water sphere mimicking the head of a rat. Methods: Calculations were performed using the finite element simulation software COMSOL multiphysics (4.3 b), using the multiturn coil definition of the magnetic fields physics. The maximum electric field at several depths from the surface were calculated as well as the half power region (HPR), surface area in which jEjjEjmax*0.707. Also the first time derivative of the magnetic field was calculated and measured (measurements provided by the manufacturer). Results: The calculated maximum electric field at the surface of the spherical rat head model was w260 V/m with the amplitude decaying with the depth (figure 1). However, at a depth of 7.5 mm from the sphere surface the maximum induced electric field was still more than 100 V/m. The HPR was located in 12.5 % of the surface area (figure 2). Further, the calculated shape and magnitude of the derivative of the magnetic field were in very close agreement with the experimentally measured field (scaling factor 0.988). Conclusion: The distribution of the induced electric field and the derivative of the magnetic field for the dedicated TMS coil design were calculated. The field exceeded 100 V/m at depths up to 7.5 mm from the surface.