PTMS55 Investigating function and structure in the ventral premotor cortex

PTMS55 Investigating function and structure in the ventral premotor cortex

14th ECCN / 4th ICTMS/DCS phosphocholine [PCho] + glycerophosphocholine [GPC]) were measured bilaterally in primary sensorimotor cortex, lentiform nuc...

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14th ECCN / 4th ICTMS/DCS phosphocholine [PCho] + glycerophosphocholine [GPC]) were measured bilaterally in primary sensorimotor cortex, lentiform nucleus, and the occipital region before and after 5 Hz TMS over the dominant motor cortex. Sixteen patients with upper limb primary dystonia were studied and compared to healthy volunteers. Results: At baseline, in patients with writer’s cramp, there was a higher GABA concentration bilaterally in the motor cortex as compared with controls. In controls but not patients, 5 Hz TMS over the left motor cortex induced an in situ-change in metabolite concentrations that depended on baseline concentration levels; i.e., increase for lower baseline levels and decrease for higher. Effects in basal ganglia were less consistent. Greater concentration decreases in NAA, mIns, and tCho were observed in the motor cortex of the patients after TMS. Conclusion: Together with previous results, our study points to a dysfunction of the GABAergic inhibitory system in dystonia. TMS-induced changes of NAA, mIns and tCho are interpreted in view of the maladaptive plasticity and abnormal membrane-related protein previously suggested in dystonia. PTMS52 Normal SICI in Parkinson’s disease: SICI using anterior posterior directed induced currents in the brain

S195 We have used collision of TMS and vestibular stimuli to investigate this possibility. Methods: The motor cortex of healthy subjects was stimulated with TMS, recording responses in axial muscles under activation with focus on the Erector Spinae back muscles. Trials alternated between TMS alone and TMS combined with an acoustic click of 0.1 ms delivered binaurally at 100 dB with an interstimulus interval of 3 ms. Results: Bilateral Motor Evoked Potentials (MEP) in Erector Spinae were seen following TMS alone in all ten subjects. When vestibular stimulation is combined with TMS there is potentiation of the responses at latencies exceeding that expected by Corticospinal transmission, markedly in the muscle ipsilateral to the side of stimulation with TMS. With added vestibular stimulus at longer latencies, Ipsilateral MEP amplitude rises and Ipsilateral to Contralateral MEP ratio rises from 0.81 to 1.73 (p = 0.0026). Conclusion: The technique allows assessment of activity in alternative motor pathways, and may serve as a biomarker for plastic change following stroke. These pathways may be targets for therapeutic intervention not routinely considered in current TMS based treatment protocols. Evidence exists to suggest the site of interaction between the vestibular and cortical stimuli may be at cortical, brainstem or spinal levels.

R. Hanajima1 , Y. Terao1 , Y. Shirota1 , S. Ohminami1 , S. NakataniEnomoto2 , S. Okabe1 , H. Matsumoto1 , R. Tsutsumi1 , Y. Ugawa2 1 Department of Neurology, University of Tokyo Hospital, Tokyo, Japan, 2 Department of Neurology, Fukushima Medical University, Fukushiima, Japan

PTMS54 Modulation of corticospinal excitability during ipsilateral contractions

Introduction: The short interval intracortical inhibition (SICI) studied by paired pulse transcranial magnetic stimulation (TMS) has been reported to be abnormally reduced in many neurological disorders, such as Parkinson’s disease (PD) and dystonia. This is usually considered to reflect abnormal GABAergic system of the primary motor cortex (M1). However, it is not always the case. We have shown the SICI studied with anterior posterior (AP) directed currents was normal even though that with PA currents was abnormal in dystonia. This may indicate that the GABAergic system of M1 is normal in dystonia. Objectives: To measure SICI in PD using AP directed currents. Methods: The subjects were 10 patients with Parkinson’s disease and 10 control healthy volunteers. The intensity of conditioning TMS was set at 90%ATM and test TMS to induce about 0.5mV MEP in relax condition. The Inter-stimulus intervals were 2 5 ms. Both AP and PA directed currents were used. Results: In PD, SICI with PA directed currents was reduced as compared with healthy volunteers. In contrast, SICI studied with AP currents was normal. Conclusions: The fact that normal SICI was induced with AP directed currents in PD suggested that GABAergic inhibitory system of M1 is normal in PD. These results are similar to those shown in dystonia. The reduction of conventional SICI using PA directed current in these diseases might be caused by composition change of I-waves contributing to MEP generation. Other explanation is that only GABAergic inter-neurons activated by PA directed currents was disturbed in PD. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.

Introduction: Strong contractions of hand muscles on one side of the body are known to increase the excitability of both the ipsilateral and contralateral corticospinal tract controlling hand muscles. Objectives: We used transcranial magnetic stimulation (TMS) to investigate whether limb position modulates ipsilateral excitability. The modulation of the facilitation could indicate to parameters involved in motor output encoding (e.g. coding based on ‘muscle mapping’ or on ‘directional parameters’). Methods: Subjects were seated with both hands in a setup that enabled measuring force of the index finger. Subjects abducted their right index finger maximally. The position of both the right and the left hand were changed independently between contractions and experimental sessions. During the contractions a motor-evoked potential (MEP) was elicited in the left first dorsal interosseus (FDI) muscle and we assessed the force vector of the twitch induced by the MEP. Results: Preliminary data (n = 6) showed that during the maximal contraction with the FDI of the right hand the twitch evoked in the left hand was significantly affected by the position of the right and left hand (interaction effect, F(4,20) = 3.682; p = 0.02). Conclusion: Although the task was similar in all contractions (index finger abduction), the size of the evoked twitch differed with hand position. Our results point to a modulation of the excitability of the corticospinal tract by the direction of the target contraction. The directions that modulate the activity of the hand muscles suggest that the corticospinal output is encoded based on the movement direction in a space referenced to the center of the body and not on the mapping of the voluntarily activated muscles.

PTMS53 Assessing alternative motor pathways using collision of vestibular stimuli and assessing alternative motor pathways using collision of vestibular stimuli and transcranial magnetic stimulation D. Hoad1 Rothwell Lab. Sobell Department. Institute of Neurology. UCL, London, United Kingdom 1

Introduction: It has been shown in both animal and human studies that vestibular inputs relaying through brainstem structures may modify the motor response to Transcranial Magnetic Stimulation (TMS) of the cortex. Effects have been seen both at the short latency typical of Corticospinal transmission, and longer latencies suggestive of interaction with Reticulo or Vestibulospinal pathways. Objectives: We have observed more frequent late responses when stimulating the damaged hemisphere of stroke patients with TMS and question whether this is a plastic adaptation to injury, accessing alternative brainstem pathways following Corticospinal tract damage.

F. Bianchi1 , T. Nijboer1 , I. Zijdewind1 1 Department of Neuroscience, University Medical Center Groningen, Groningen, Netherlands

PTMS55 Investigating function and structure in the ventral premotor cortex L. Cattaneo1 , G. Barchiesi1 Center for Mind/Brain Sciences, University of Trento, Trento, Italy

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Introduction: The ventral premotor cortex (PMv) is known to exert shortlatency effects on the hand-related primary motor cortex (M1). There is however considerable ambiguity in recent research about what part of the frontal lobe actually supports the functions that are attributed to PMv. Its definition ranges from the ventral precentral gyrus, to the precentral sulcus, or to the caudal part of the inferior frontal gyrus. On the other hand, the most various functions have been mapped onto the region broadly defined as PMv, including visuomotor control of grasping, action understanding, speech production or semantic coding of language. Objective: Here we aimed at defining what part of the ventro-caudal part of the frontal lobe interacts via short-latency connections with the hand-associated primary motor cortex. Methods: We used a dual coil technique with one coil positioned on M1 and the other moving on a 24 points grid over the lateral portion of

S196 the frontal lobe and Rolandic region. We applied interstimulus intervals of 4 and 7 ms. The whole experiment was conducted at rest and during visually-guided manipulation of an object. Results: The PMv spots that exerted a short-latency effect on M1 were distributed mainly along the precentral sulcus. At rest the effects of PMv stimulation were mainly inhibitory. During manipulation we observed clear inversion of the effect, with M1 facilitation in some spots. The location of facilitatory spots varied greatly between subjects, from a dorsal position bordering with the inferior frontal sulcus to more ventral positions. Conclusion: These results show that within the lateral portion of the frontal lobe only a portion of cortex actually communicates with shortlatency connections with M1. Within this region the functional aspects are consistent and predictable between subjects (i.e. inhibitory connections turning facilitatory during active tasks) however its topographical organization seems highly variable between individuals. PTMS56 Volume conductor modeling of the effects of transcranial magnetic stimulation A.M. Janssen1 , T.F. Oostendorp2 , S.M. Rampersad1 , C.H. Wolters3 , D.F. Stegeman1 1 Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Department of Neurology/Clinical Neurophysiology, Nijmegen, Netherlands, 2 Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Department of Cognitive Neuroscience, Nijmegen, Netherlands, 3 Insitute for Biomagnetism and Biosignalanalysis, University of M¨ unster, M¨ unster, Germany Introduction: To optimize the effect of Transcranial Magnetic Stimulation (TMS), a clear understanding of the underlying mechanisms is needed. Part of that understanding concerns the estimation of current flow in brain structures induced by the magnetic field. In order to achieve this, a precise volume conductor simulation model of the current induced in the human head has to be developed. Objectives: The objective is to model the induced current distribution caused by TMS using realistic geometries and properties of the head and the stimulation coil. Methods: Work from literature shows that solving the bioelectric problem for TMS with the finite element method (FEM), applied to a realistic head model, is a promising method. In this study this forward bioelectric problem was mathematically solved using a realistic head model based on geometry and conductivity, acquired from Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) measurements. The model allows inhomogeneous and anisotropic structures to be implemented. In addition to precise head geometries and conductivities, it is also important to model the magnetic field as realistically as possible. Therefore, for each element in the head model the magnitude and the direction of the rapidly changing magnetic field were calculated using the precise geometry and position of the stimulation coil relative to the head. Results: The FEM model has been completed. Preliminary simulation results show that it describes a precise current distribution in the human head giving insight in the relative sensitivity to various parameter choices. Results including these relative effects of several human head and coil properties will be presented. Conclusions: Our model can realistically describe the induced current distribution caused by TMS. It can be used to calculate the relative effect of several properties of the human head, for example the important influence of the cerebrospinal fluid and the gray matter boundary geometry. PTMS57 A high resolution simulation study of the time-dependent effects of tissue anisotropy in transcranial magnetic stimulation N. Toschi1 , T. Welt2 , M.E. Keck3 , M. Guerrisi1 1 Medical Physics Section, Faculty of Medicine, University of Rome atsklinik Z¨ urich, “Tor Vergata”, Rome, Italy, 2 Psychiatrische Universit¨ Zurich, Switzerland, 3 Center of Neuroscience Research Zurich (ZNZ) and Privatklinik Schl¨ ossli, Oetwil am See/Zurich, Zurich, Switzerland Introduction: The importance of explicitly involving deep brain structures in therapeutic strategies involving Transcranial Magnetic Stimulation (TMS) is becoming increasingly evident through deep brain stimulation (DBS) studies as well as deep transcranial stimulation (H-Coil). Diffusion

Poster presentations: TMS meeting poster session Tensor Imaging (DTI) has recently revealed the involvement of white matter alterations in a number of pathologies (AD, MS, ALS, Epilepsy, Parkinson’s) for which the therapeutic efficacy of TMS is being explored. The spatial distributions and time evolutions of conductive phenomena induced in brain parenchyma are not determinable in-vivo, and available models have not been able to combine satisfactory resolution with descriptions of white matter anisotropy and time-domain effects. The optimal condition-specific protocol, including sham stimulation conditions, remains largely undetermined. Objectives: To perform a high-resolution (below 1 mm3 ) DTI-based characterization of the anisotropy-related, time-dependent tissue-field interactions in TMS through high-performance parallel computing. Methods: DTI, T1 and T2 scans from healthy volunteers where converted into dielectric property maps through convolution-based tensor field interpolation and known cross-property relations. The electromagnetic problem was solved through an adequate finite-difference time-domain scheme on a high-performance GPU. Results: Establishment of a sub-millimeter resolution computational framework for quantifying TMS outcome. Demonstration of a significant influence of preferential conduction directions on induced electric field, particularly under high-permittivity assumptions. Quantification of predictability, focality, and reproducibility of stimulation under controlled parameters. Conclusions: Informed and targeted treatment delivery (i.e. optimal disease specific coil and setup variables) can only be performed through computer-assisted, disease-specific quantification of the impact of tissue degeneration and (re)organization on stimulation patterns. PTMS58 Neurophysiological properties of resting state fMRI functional connections V. Giacobbe1 , M. Cercignani2 , S. Bonnì1 , G. Bucchi1 , C. Caltagirone1,3 , M. Bozzali2 , G. Koch1,3 1 Laboratory of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179 Rome, 2 Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Via Ardeatina 306, 00179-Rome, 3 Department of Neuroscience, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy Introduction: Functional connectivity is defined as the temporal dependency of neuronal activation patterns of anatomically separated brain regions. Many neuroimaging studies are exploring functional connectivity by measuring the level of co-activation of resting-state fMRI time-series between brain regions. The so-called default mode network (DMN) has been identified as a neuronal network showing a coherent pattern of activation (functional connectivity). Objectives: We recently developed a new method for investigating functional connections between the posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) non-invasively in humans, using a bifocal transcranial magnetic stimulation (TMS) paradigm. We aimed to investigate whether fMRI measures of cortico-cortical connectivity may share a causal relationship with the physiological properties of these circuits. Therefore we combined resting-state fMRI with bifocal TMS to detect potential correlations between these different measures. Methods: A conditioning TMS pulse was applied over PPC shortly before a test pulse over the hand area of M1. At appropriate interstimulus intervals, the motor response evoked by the M1 pulse was modified, indicating the presence of functional interactions between the two sites. As for resting state fMRI data, these were preprocessed using statistical parametric mapping, and in-house software implemented in Matlab. We used the independent component analysis to identify, on a subject by subject basis, regions belonging to the DMN. Results: We found a remarkable correlation between TMS and DMN measures in different cortical sites that likely form part of the PPC-M1 connection, such as the angular gyrus, the ventral premotor cortex, the dorsal premotor cortex and M1 itself. Conclusions: Resting state fMRI may be an effective method to investigate some specific neurophysiological circuits. The combined neurophysiological/imaging approach could increase the impact of these methods and allow to better characterize the anatomo-functional properties of brain connections.