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Mar Cortes

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Mar Cortesa,b, Alejandra Climenta, Laura Dubreuil Vallc, Giulio Ruffinic  Douglas Labara, Dylan Edwardsa a. Non invasive Brain Stimulation and Human Motor Control Laboratory, Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamaroneck Avenue, 10605, White Plains, NY, USA.b. Universitat de Barcelona, Barcelona, Spain. c. Neuroelectrics Corporation, Cambridge (MA), USA. Corresponding author:Mar CortesNon invasive Brain Stimulation and Human Motor Control Laboratory, Burke Medical Research Institute, Weill Medical College of Cornell University, 785 Mamaroneck Avenue, 10605, White Plains, NY, USA.mac2083@med.cornell.eduPhone: +1 914 368 3181 Abstract: (250)[MC1]  Background: Existing strategies to enhance motor function following Spinal Cord Injury (SCI) are suboptimal leaving patients with considerable disability. Available evidence suggests that transcranial direct current stimulation (tDCS) is a promising method to improve motor dysfunction. How tDCS affects resting brain activity monitored by EEG is little explored. Objective: Investigate the effects of anodal tDCS on brain signaling (EEG) and neurophysiology (TMS) when targeting forearm muscles below the level of the lesion in chronic SCI subjects. Methods: We conducted a randomized, single blind, sham-controlled, cross-over study in seven chronic SCI subjects with cervical lesions. We investigated the effects of 20-minute anodal tDCS applied over the left primary motor cortex (M1) on electroencephalography (EEG) power spectrum density, coherence and frequency band power. Subjects were randomized to receive either 1mA or sham stimulation.  The EEG data acquisition pre and post stimulation comprised 5-minute takes of 24 bit, 500 S/s 8-channel EEG using StarStim Ag/AgCl EEG electrodes (at F3, F4, Cz, C4, P3 and P4; and Pi Ag/AgCl electrodes at C3, anode, AF8, return). Results: In comparison to sham stimulation, 20-minutes of active 1mA tDCS induced a pattern of faster activity around the anodal stimulating electrode, and slowing activity near the return electrode in the frequency (full band) and mean power domain (gamma band). In addition, tDCS increased coherence in the fastest bands (gamma, beta 2) and decreased coherence in slower frequency bands (theta, SMR), with no relation with brain topography or the stimulation electrode polarity. Conclusions: These findings show that tDCS is capable of inducing modulation of ongoing oscillatory brain rhythms captured by EEG, in spinal cord injury patients. The combined use of EEG and tDCS sets the stage for optimizing tDCS protocols targeting motor cortex and may have application in treatment of motor dysfunction and chronic pain.  Key words: spinal cord injury, EEG, tDCS, motor cortex, TMS Abbreviations:    Introduction[JC2]  Transcranial direct current stimulation (TDCS) delivered over primary motor cortex (M1) can increase or decrease corticomotor excitability as determined by the amplitude of the motor evoked potential (MEP) from stimulating M1 with supra-threshold transcranial magnetic stimulation (TMS). The effect on MEP amplitude depends on the duration and intensity of stimulation and the polarity and spatial arrangement of the TDCS electrodes, and these effects can persist for up to an hour after TDCS is ceased. It is assumed that the TDCS after-effect results from some form(s) of neuromodulation at the cortical level such as synaptic potentiation or depression, or effects on ion channels. However, further insight into the cortical mechanisms in the human is limited experimentally. The electroencephalogram (EEG) measures far-field potentials from synchronized neural populations over cortical regions that extend beyond M1, and so offers a method for measuring the effect of TDCS on neural activity across the cortex.  In particular, such measurements do not depend on spinal cord conduction and alpha-motoneuron activation, which is the case for MEP recordings. This could have advantages for determining the effect of TDCS at the cortical level in spinal cord injury (SCI). While most SCI studies focus on the level of injury, there is increasing interest in the compensatory changes that might occur in the cortex, and whether they might facilitate or impede recovery. In the present study we measured the effect of EEG after 20 min of anodal or sham TDCS applied to the dominant M1 in chronic cervical SCI. We show that there are changes in EEG power, frequency and coherence that are spatially-related to the TDCS electrode configuration, but that spread widely across the hemispheres. [MC3]  Materials and methods Participants and study designThe randomized, single blind, sham controlled, cross over study was conducted on seven chronic SCI subjects, all males with an average age of 51.14 ± 10.57 years (mean ±SD, range 34 to 65 years). Participants presented traumatic SCI at the cervical level (C4-C8); some degree of motor function in wrist extension (score 1-5 over 5 on the Medical Research Council (MRC) scale for motor strength in the right extensor carpi radialis (ECR) muscle); chronic injury (>9 months after injury); and tolerance to sitting upright for at least one hour (see Table 1 for baseline characteristics). Patients were excluded if they presented with: progressive neurodegenerative disorder; concomitant traumatic brain injury or stroke; clinically significant cognitive impairment; medically unstable; change in medication during the study; or presented contraindications to brain stimulation (history of seizures/epilepsy, presence of metallic implants in the brain, pacemaker, pregnancy). The subjects were randomized in two groups depending on whether they were receiving stimulation or not:  a) Sham or control group, b) 1mA or active group. We investigated the effects of 20-minute anodal t-DCS applied over the primary motor cortex (M1) on: a) quantitative electroencephalography (EEG) power spectrum density, coherence and frequency band power. At Baseline we collected: clinical and functional evaluations were performed prior the brain stimulation intervention, and included the upper extremity motor score (UEMS), American Spinal Injury Association impairment scale (AIS), spinal cord independence measure (SCIM III) and visual analog scale (VAS) pain questionnaires. [DE4]  The study was approved by the Burke Medical Rehabilitation Institutional Review Board and conformed to the standards set out by the 1964 Declaration of Helsinki.                  AddTable 1 Transcranial direct current stimulation (t-DCS) interventionParticipants remained seated in their own wheelchair or were provided with a comfortable chair. The StarStimNE noninvasive wireless t-DCS/EEG neurostimulator (NE Neuroelectrics®, Barcelona, Spain) was used to both record EEG data and deliver the direct current sequentially. The StarStimNE neurostimulator included a wireless neoprene cap, based on the International 10-20 system, which was placed on the participants’ heads by aligning the central CZ electrode position with the vertex (intersection of nasion-inion and inter-aural line mid-point).Small Ag/AgCl gelled electrodes, with a surface contact area of 3.14 cm2 specific to the StarStimNE device (Pi electrodes, Neuroelectrics®), were placed over the left M1 at C3 (anode) and contralateral supraorbital area, (AF8; cathode) (Figure 1). The electrodes were connected to a control box device, which was wirelessly connected to a computer and communicated with the NIC software (version 1.2, Neuroelectrics®).  Add Figure 1 During anodal stimulation, direct current was delivered from a current-control circuit in the battery-driven stimulator within the control box device. The current was set at 1mA intensity and applied for 20 minutes. [DE5] For the sham stimulation, electrodes were placed in the same position and participants received a short ramp (30sec total up / down[DE6] ) at the beginning and end of the stimulation period.  Electroencephalography (EEG)The StarStimNE multichannel wireless device (NE Neuroelectrics®, Barcelona, Spain), which allows for simultaneous electroencephalography (EEG) and tDCS[DE7] , was used to record EEG data. The EEG data consisted of 5-minute takes (pre and post stimulation) with 24 bit resolution, 500 S/s 8-channel EEG collected with StarStimNE Ag/AgCl EEG electrodes (geltrodes, NE022; positions at F3, F4, Cz, C4, P3 and P4; Pi stimulating electrodes at C3 and AF8), based on the International 10-20 system, with the cap aligned to the central CZ electrode position (vertex).[DE8]  The electrodes were connected to a control box device, which was wirelessly connected to a computer and communicated with the NIC software (version 1.2, Neuroelectrics®). Transcranial magnetic stimulation (TMS) Electromyography (EMG): A bipolar surface EMG electrode (1 cm diameter, 2 cm inter-pole distance; Biometrics Ltd, UK) was placed over the right ECR muscle, with the forearm relaxed in a pronated position and supported by a cushion. The EMG activity was amplified and filtered on site (x1000 gain, band-pass filter 20-460 Hz; SX230-1000), digitized at 2 kHz (CED 1401, Cambridge Electronic Design, Cambridge, UK) and stored for offline analysis using Spike 2.6 software. Measurements were performed at rest. During the experiment, free running EMG was continuously monitored with visual feedback of EMG to ensure complete muscle relaxation.The right ECR muscle was selected for clinical relevance; where restoration of motor function in this muscle can help increase independence in quadriplegic subjects with activities of daily living.  Transcranial Magnetic Stimulation (TMS): A figure-of-eight coil (Model DB-80, Tonika Elektronik A/S, Farum, Denmark), connected to a MagPro X100 series (MagVenture A/S, Farum, Denmark) magnetic stimulator, was placed congruent with the head and the handle rotated 45° lateral from mid-sagittal so as to induce currents in the brain approximately perpendicular to the central sulcus. Resting motor threshold (RMT) was established at C3, and was defined as the minimum TMS intensity required to elicit a reliable MEP in the contralateral ECR amplitude of >50 µV in at least 50% of consecutive trials.[DE9]  EEG data processing/statistical analysisResting quantitative EEG and corticospinal excitability (transcranial magnetic stimulation; MEP) were recorded before (PRE) and at the end (POST) of each intervention. Quantitative EEG measures included: mean power, mean frequency and mean coherence. The three measures were normalized as the percentage change between PRE and POST stimulation, for each frequency band and electrode. The frequency bands were defined as: Theta= [4 8] Hz, Alpha-1=[8 10] Hz, Alpha-2=[10 12] Hz, SMR=[12 16] Hz, Beta-1=[16 25] Hz, Beta-2=[25 35] Hz, Gamma=[35 40] Hz.The mean power is defined as the average power in uV2 in a given frequency band. The mean frequency is defined as the average frequency in a given band, weighting each frequency value by their corresponding power at that frequency. The mean coherence of a given electrode is defined as the average coherence of this electrode with all the other ones (i.e., the similarity of that signal with all the other electrodes).--> Giulio to revise - DONEThe EEG data were referenced to the average of all 8 electrodes. An automated quality check of the data was then carried out using 8 sec epochs. Epochs have been rejected if they do not meet quality criteria (too high mean power at full band or line noise, or motion artifacts as detected by the built in accelerometer). PSD changes and coherence analysis was carried out for each quality passed epoch. Average PSD’s and coherence have then been computed for each subject.EEG data were discarded from analysis for channels presenting bad signal quality during the entire 5-minute recording. Those subjects that did not have more than 5 valid channels were completely discarded. After the discarding process, in order to have the same subjects in all the conditions, 7 subjects were analyzed for Sham and 1mA.Resting MEP amplitude (peak-to-peak; ECR muscle) was measured following single-pulse TMS (10/12) set at 120% [DE12] of the RMT over the C3[DE13] . Raw and normalized values were used for analysis[DE14] . Results are presented as mean ± standard deviation (SD), and standard error of the mean (SEM)[DE15] .After normalizing the EEG features as the percentage change between PRE and POST stimulation, statistical comparison between Sham and Active (1mA) stimulation has been done. The p value in the T tests has been calculated with a Wilcoxon one-tail T test with the assumption of paired samples. Changes are considered statistically significant when p =< 0.05. PLEASE ADD THE STUDY DATA ANALYSIS – GIULIO / LAURA --> Described above Results Effects of tDCS on EEGNormalized pre-post EEG power, frequency and coherence for those subjects who received 1mA tDCS compared to those who received sham stimulation shows: a) significant increase of the mean power in the 1mA group in the Gamma frequency band under C3 (p=0.0035), the anodal stimulating electrode; b) a significant increment in the active group of mean frequency around the anode (stimulating) electrode (C3, F3) (p=0.0047) with a decreased mean frequency in the Alpha band near the return electrode (P4) (p=0.035); and c) significantly increased mean coherence in the active group in the fastest frequency bands Beta2 under Cz and C4 (p=0.007), Gamma band under Cz electrode (p=0.0023), C3 electrode (p=0.0006) and C4 electrode (p=0.0006), and SMR band under C3 electrode (p=0.05). LAURA – ADD THE TYPE OF TEST USED FOR THE RESULTS AND THE P VALUES OBTAINED --> Described  above Effects of tDCS on Corticospinal excitabilityBaseline values for resting MEP amplitude were similar between interventions (average: 0.37±0.05 mV; mean±SEM). No significant changes were observed for 1 mA a-tDCS or sham. The stimulation intensities used to obtain the RMT were not significantly different between 1 mA (64±17% MSO) and sham (66±16% MSO). All participants presented MEP responses.   Discussion1. tdcs does modulate EEG in SCI population. 2. The effect of the TDCS in EEG is location specific and band specific. 3. The fastest bands are more affected. Augmented power and frequency of fast bands (Gamma and B2) under the anode electrode - there is more fast activity under the anodal electrode.  Why is this?3.1. Anodal stimulation leads to increased spontaneous neuronal firing, increase motor cortex excitability. So we would expect more fast activity and higher amplitudes under the anode electrode. 3.2. Brain activity changes (increase fast band) are related to motor learning – changes in Mu rhythm (preparation for movement, getting ready for movement). This is shown in the coherence increase of SMR band under the stimulating electrode.  MAR – ALL OF THE ABOVE 3.2.1. Is there are connection between C3 and P4 in resting state brain? Why is alpha decreased significantly in P4 (cortex parietal) in the contralateral hemisphere.  CONECTIONS BETWEEN MOTOR CORTEX AND SENSORY MOTOR CORTEX?? – JANA 3.3. Anodal tDCS makes C3 to be more related to the rest of the head, by increasing the connectivity of the SMR under the stimulating electrode. INTERPRETANTION OF THIS POINT TO GIULIO/LAURA, ANYTHING PUBLISHED BEFORE?Here you have a reference using EEG coherence: Rafael Polanıia, Michael A. Nitsche, and Walter Paulus. "Modulating Functional Connectivity Patterns and Topological Functional Organization of the Human Brain with Transcranial Direct Current Stimulation". Human Brain Mapping (2010). 3.4. This is an excitability independent change (no TMS change associated). Can EEG pick up changes in the brain than TMS cannot?                                                       LABAR? Conclusion These findings show that t-DCS is capable of inducing modulation of ongoing oscillatory brain rhythms captured by EEG, in spinal cord injury patients. The combined use of EEG and t-DCS sets the stage for optimizing t-DCS protocols targeting motor cortex and may have application in treatment of motor dysfunction and chronic painFigures 
The corticomotor projection to liminally-contractable forearm muscles in chronic spinal cord injury: A transcranial magnetic stimulation studyRunning Title: Cortico-motor conduction in chronic SCI Mar Cortes, MD1,2,3, Gary W Thickbroom, PhD1, Jessica Elder, PhD4, Avrielle Rykman, OT1, Josep Valls-Sole, MD, PhD3,5, Alvaro Pascual-Leone, MD, PhD6, Dylan J Edwards, PhD1,2,4,6  1 Non-invasive Brain Stimulation and Human Motor Control Laboratory, Burke Medical Research Institute, White Plains, NY2 Neurology Department, Cornell University, New York, NY3 Universitat de Barcelona, Barcelona, Spain 4 Epidemiology Department, Cornell University, New York, NY5 EMG and Motor Control Unit, Neurology Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain6 Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.Corresponding Author:Mar CortesNon-invasive Brain Stimulation and Human Motor ControlBurke Medical Research Institute785 Mamaroneck Avenue, White Plains, 10605, NYPhone: +1 914 3683181         Fax: +1 914 597 2796 Email: mac2083@med.cornell.eduAbstractStudy design: A cross-sectional study in chronic spinal cord injury (SCI)Objective: To determine the corticomotor projection and motor cortex organisation in forearm muscles with a motor power (MP) of one (liminal voluntary activation).Setting: Burke Medical Research Institute, White Plains, New York, USAMethods: We identified ten people with chronic SCI (cSCI) who had a wrist flexor or extensor muscle with a motor power (MP) of 1/5. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) over the primary motor cortex of the hemisphere contralateral to the targe muscle. We measured resting motor threshold (RMT), corticomotor latency (LTY), MEP amplitude (AMP) and performed cortical motor mapping to determine the optimal site (OPT) and map area (AREA). Results were compared to data from 18 controls.Results: A MEP in the target muscle was observed for all cSCI cases. LTY was normal, while corticomotor excitability (as determined by RMT and AMP) was reduced in about half of the group. The OPT site of the motor maps was within control range for all cSCI cases, while AREA was reduced in 3 cases.Conclusions: Corticomotor conduction and cortical topography were appreciably-normal despite only liminal activation of the target muscle with voluntary effort. Muscles with these characteristics may benefit from a targeted rehabilitation program even in the chronic phase after SCI. IntroductionA cervical spinal cord injury (cSCI) can result in paralysis or severe motor deficits in the upper and lower extremities that can have a devastating impact on independence and quality of life (ref: Welch, Lobley 1986).  In the upper extremities, recovery of function in the wrist flexors and extensors is important as it can lead to improvements in arm and hand function (ref: Ditunno, Herbison, 1987; Hanson, Franklin, 1976).  The American Spinal Injury Association (ASIA) Impairment Scale (AIS) is widely used to classify impairment (motor and sensory) after spinal cord injury. For the assessment of upper limb motor power, the AIS scale uses the Medical Research Council (MRC) scale for motor power (MP) and pools this for 5 functionally relevant movements (including wrist extension). The MRC scale ranges from 0 to 5, with a MP of 1 defined as a trace of muscle contraction or fasciculation, but no overt movement about the joint. We recently described a cSCI case study in which corticospinal conduction to the wrist flexors and extensors was remarkably preserved, even though wrist MP was only 1/5 (ref: Edwards et al, 2013; Curt, Dietz, 1999). Using transcranial magnetic stimulation (TMS), we reported motor evoked potentials (MEPs) of normal amplitude and latency for these wrist muscles. This observation suggested that supraspinal motor-related networks could be implicated in functional weakness after cSCI. However, the changes that might occur in these networks in response to cSCI are not well understood. It is known that spinal cord injury can result in cortical atrophy (ref: Jurkiewicz et al 2006; Paxinox and Watson, 2005; Ghosh et al 2010) and there is evidence for cortical reorganisation from functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and electroencephalographic (EEG) studies (Kokotilo el at, 2009).  TMS can be used to map the corticomotor projection from primary motor cortex (M1) to a target muscle (Wilson, 1993) and provides another opportunity to investigate cortical reorganisation. While TMS mapping has been used to identify reorganisation of muscles innervated above the level of the lesion (Levy et al), there have been no such studies of severely impaired muscles at the level of the lesion. In the present study, we have measured corticomotor conduction and performed TMS mapping in a group of 10 people with cSCI and a MP in a forearm muscle of 1/5. Our aims were to determine how corticomotor conduction was affected in people with a MP of 1/5, and to determine whether the cortical maps were normal or showed signs of reorganisation. Methods ParticipantsTen people with cSCI volunteered to participate in the study (Table 1). All met the following inclusion criteria: age 18-70 years; chronic injury (>1 year after injury); cervical injury level; traumatic lesion; motor complete or incomplete; MP of wrist extensor or flexor muscles 1/5; no evidence of trauma-related brain injury; no contraindications for TMS: no history of seizure; medically stable. A second investigator independently confirmed the MP score. All cSCI participants were right-handed prior to injury and remained so thereafter. None of the participants had a history of neurological or psychiatric disorders. Eighteen right-handed healthy participants (24-51years of age; 8 male) without a history of neurological or psychiatric illness were recruited as a control group. The Institutional Review Board of the Burke Rehabilitation Hospital approved the experimental protocol, and all subjects gave written informed consent prior the experiment. Motor powerThe MP of the Extensor Carpi Radialis (ECR) and Flexor Carpi Radialis (FCR) muscles on the left and right sides was scored independently by two neurologists. The muscle identified by both scorers as having a MP of 1 was the target muscle for the remainder of the study.  EMG RecordingBipolar surface electromyography (EMG) electrodes  (1cm diameter, 2cm inter-pole distance, x1000 gain, band-pass filter 20-400Hz) were placed over the belly of the target muscle. EMG activity was recorded by Biometrics electromyography (Biometrics Ltd, UK), and signals were fed into CED 1401 using Spike 2.6 for further off-line analysis. During the experiments, EMG activity was continuously monitored with visual feedback to ensure complete muscle relaxation.  An estimate of maximum voluntary contraction (MVC) in the cSCI group was obtained by recording short periods of EMG while the participant attempted a maximum muscle contraction. Three 0.5 second epochs of EMG were acquired, and the average root-mean-square EMG calculated. Three 0.5 second epochs of resting EMG were also acquired as an estimate of signal noise. TMS measurements were taken for the ECR and FCR muscles on the left and right sides in the 18 controls.  Transcranial Magnetic Stimulation (TMS)SCI participants were seated in their own wheelchairs and wore a snugly-fitting pre-marked cap with sites marked in spacings of 1cm in latitude and 2cm in longitude in relation to the vertex and inter-aural line (Thickbroom et al., 1999; Wilson 1993). A figure-of-eight coil (DB-80, Tonika Elektronik A/S, DK-3520, Denmark) was connected to a MagPro magnetic stimulator (MagVenture). The coil was manually positioned on the scalp over the expected location of the contralateral primary motor cortex (M1), with the handle pointing backwards at an angle of 45 degrees to the midline (Brasil Neto, 1992). The optimal site was established by a search pattern at suprathreshold intensity to determine the location yielding the largest MEPs. Resting motor threshold (RMT) was measured at this site and was defined as the minimum intensity (2% steps in stimulator output) required to elicit at least 3 motor evoked potentials (MEPs) with a peak-peak amplitude >50uV in 5 consecutive trials (ref Rossini 2009, Rothwell 1999).  For the remainder of the experiment, TMS intensity was set to 1.2xRMT.  Twenty MEPs were recorded at the optimal site at this intensity. Mean MEP peak-peak amplitude (AMP) and MEP onset latency (LTY) were determined from these data by manual cursoring. Motor Cortex MappingFive stimuli were delivered at a frequency of 0.2Hz at each stimulation site starting at the optimal site and then successively stimulating adjacent sites until no MEP was found (<50uV amplitude). To maintain consistency in coil orientation as it was repositioned over the scalp, the coil was held in the parasagittal plane for mapping. Maps were generated by fitting a continuous function to the mean peak-to-peak MEP amplitude in each scalp site (Wilson 1993). The latitude (LAT) and longitude (LONG) at which the map had its maximum amplitude was determined. LAT was expressed as the distance in cm from the vertex, and LONG the distance in cm anterior (+ve) or posterior (-ve) to the inter-aural line. To avoid biasing map area (AREA) by small MEPs on the periphery, AREA was calculated from the region of the map with an amplitude greater than 1/8 of maximum.  Statistical Analysis A wilcoxon rank-sum was used to test for an effect of SIDE (left, right) and MUSCLE (ECR, FCR). A two-way ANOVA was used to assess for an interaction between SIDE and MUSCLE. From the control data, 95% confidence intervals were determined for each parameter (RMT, AMP, LTY, LAT, LONG, AREA). The lower limit (LL) was 2 standard deviations (SD) below the mean and the upper limit (UL) was the mean plus 2xSD. The AMP data was skewed, and log transforms were used to establish LL and UL. SCI data for each participant was compared to control ranges.Results SCI characteristics are given in Table 1. The mean age was 42.4±16.5 years (SD; range 17-70 years of age; 7 M, 3 F). The mean period following injury was 6.1±8.2 years (range 1.8 to 29 years). Eight of the SCI group had incomplete lesions and two had complete lesions. Two subjects were classified as motor-sensory complete (AIS A), five as motor complete but sensory incomplete (AIS B), and three as motor and sensory incomplete (one as AIS C). All participants had severe upper and lower limb impairment. Left-sided muscles were studied in five participants. The mean age of the control group was 36.1 ± 6.8 (SD, range 24-51years).   For the control group a Wilcoxon rank-sum test revealed no effect of SIDE (for all parameters) but an effect of MUSCLE for most parameters (p<0.05). As a result, data was pooled for the left and right sides and normal ranges established separately for the ECR and FCR (see table 2).  For the SCI group, an analysis using two-way Anova revealed there were no effects for SIDE, MUSCLE or SIDExMUSCLE. Correspondingly, SCI data from either side was compared to the control ranges for ECR and FCR.  Corticomotor Excitability and Conduction A response in the target muscle to TMS was observed for all cases in the SCI group. In general, corticomotor conduction times were normal while corticomotor excitability (as determined by motor threshold and MEP amplitude) was reduced in about half of the group.  RMT was above control range for 6/10 cases (between 2% and 38% of stimulator output above UL). AMP was below control range for the ECR (by an average of 17%) but within control range for the FCR. LTY was normal for all but one case that was delayed by 0.3ms. RMS ranged from 0.008-0.017 uV for ECR and 0.007-0.015 uV for FCR (mean for combined muscles 0.011+0.004 uV). Mean resting RMS was 0.007+0.002 uV. There was no correlation between RMS during an attempted MVC and AMP (p=0.22).  Corticomotor Mapping TMS maps could be obtained for all SCI cases. Figure 1 gives MEP waveforms and maps for a representative case from the SCI group and the control group. Table 2 gives the control ranges for each parameter and table 3 provides the results for each case in the SCI group.  LAT and LONG were within control range for all SCI cases (Figure 2). AREA was reduced in the FCR for 3 cases (2 marginally).  Discussion It was possible to determine a RMT, record a MEP and measure a motor map for a forearm muscle in all cases from this group of chronic cervical SCI. The unifying feature in the group was the selection of a target muscle with a MP of 1/5. We show that corticomotor conduction through the level of the spinal injury is remarkably patent and that the topographic origins of this projection in M1 are normal. The results indicate that in the chronic phase after injury, and in muscles with only liminal voluntary activation, there can remain a significant neurophysiological substrate that could be a target for rehabilitation. We have previously reported that corticomotor conduction can be within control values in a case study of chronic cervical SCI (Edwards). The present study generalises this finding by showing that it is not rare to find patent corticomotor conduction in muscles with only liminal levels of voluntary activation in the chronic phase after SCI.  Corticomotor conduction time was within control range for all but one SCI case that was marginally delayed. This is in contrast to some previous studies that indicate conduction through the lesion is often delayed (ref: Calancie, Alexeeva et al 1999; Harkema, McKay, Green 2012; Awad, Carmody, Lin, 2013). However, spinal cord injury is expected to have diverse effects on corticospinal conduction depending on the nature of the lesion. In our cSCI group, selected to have a degree of commonality (chronic and stable, cervical lesions, forearm wrist extensors/flexors, MP=1), we find that the fast-conducting mono-synaptic pathway to the target muscles can be relatively normal. While RMT was increased and AMP decreased in about half of the cases, in many these data were not greatly outside of control range. Across the group, we mostly observed these abnormalities for the ECR rather than the FCR muscle. In the control group we found inter-muscle differences, with the ECR having a lower RMT and higher AMP than the FCR. This difference was not seen in the SCI group, presumably because RMT was increased and AMP reduced mostly just for the ECR muscle. The reason for this is not certain, however it could be related to differences in the corticospinal projection to wrist flexor and extensor muscles. It is known that wrist extension can be severely affected in SCI (ref?), and the wrist extensors are target muscles in the AIS scoring system (ref?). The retention of corticospinal conduction through the lesion is consistent with anatomical studies that show there are usually spared axons across a lesion (Bunge et al 1997; Kakulas - Dylan). However, less is known about the corticomotor pathways these axons serve. The TMS mapping data suggest that the spared axons that give rise to the MEP originate from the expected forearm representation in M1. It is known that the cerebral cortex is remarkably adaptable, and that cortical and subcortical lesions can lead to functional reorganisation (refs). Previous studies of cortical reorganisation after SCI have mostly employed functional imaging techniques such as functional MRI and PET (Kokotilo el at, 2009).  These studies require voluntary activation of a target limb, often targeting muscles proximally to the lesion, that can recruit multiple brain regions and involve polysynaptic pathways not accessible to TMS. The present study was performed in forearm muscles with MP = 1, and indicated that the corticospinal neurons giving rise to the MEP in these muscles had a normal cortical topography. We cannot say whether this would be true in higher-functioning proximal muscles, where reorganisation might take place as a result of use-dependent plasticity, or in muscles of the lower extremity.  Perhaps the most intriguing finding is that even for those muscles with normal corticomotor conduction and cortical topography, the muscles could only be liminally activated under voluntary control, even when participants were asked to do a maximal effort. The underlying cause of this functional paralysis is not certain, and may perhaps involve a learned disuse. If so, the present results increase confidence that clinically-meaningful improvement in function might be achieved with a suitable rehabilitation program. Objective data of corticomotor conduction, such as provided by TMS, may also increase the likelihood of success if communicated to participants. In conclusion, in our cSCI group, targeting a forearm muscle with MP = 1/5, corticomotor conduction and cortical topography were appreciably-normal despite only liminal activation with voluntary effort. This suggests that muscles with these characteristics may benefit from a targeted rehabilitation program even in the chronic phase after SCI. In the absence of TMS, our data suggests that further rehabilitation of muscles with a MP of 1/5 might be indicated. Demonstration of a good cortical-motor connection by TMS may be a fillip to people struggling with recovery of weakly-activated muscles after SCI.