Transcranial magnetic and electrical stimulation compared: Does TES activate intracortical neuronal circuits?

OBJECTIVE: To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings. METHODS: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse). RESULTS: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9 ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3 ms) and facilitation at longer ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5 ms). CONCLUSIONS: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. SIGNIFICANCE: TES is a suitable tool to induce intracortical inhibition and excitation.     

Impairment of callosal and corticospinal system function in adolescents with early-treated phenylketonuria: a transcranial magnetic stimulation study

The transcranial activation and the conduction properties of corticospinal and callosal neurons were investigated in 12 early-treated adolescents (aged 17.3, SD 3.5 years; range 14–27 years) with phenylketonuria (PKU) by focal transcranial magnetic stimulation (fTMS) of the motor cortex. The patients had no functionally relevant motor disturbances in daily life or on clinical testing. Corticospinally mediated excitatory (response thresholds, amplitudes, central motor latencies) and inhibitory [duration of postexcitatory inhibition (PI)] effects of fTMS were investigated in contralateral hand muscles. Transcallosal inhibition (TI) (onset latency, duration, transcallosal latency) of tonic electromyographic (EMG) activity was tested in ipsilateral muscles. Peripheral motor latencies were determined for responses elicited by magnetic stimulation over cervical nerve roots. Ten normal subjects served as controls. Since in all PKU patients, central and peripheral motor latencies were normal, no neurophysiological indication of a demyelination of corticospinal or peripheral motor fibres was found. However, cortical thresholds of corticospinally mediated responses were increased (52.1, SD 11.6% versus 35.0, SD 7.4% of maximum stimulator output; P < 0.05; n = 24 hands) and their amplitudes reduced (2.9, SD 1.4 mV versus 6.1, SD 1.5 mV, P < 0.05). The duration of PI was shortened (132, SD 53 ms versus 178, SD 57 ms; P < 0.05). TI was absent in 37.5% of the investigated hands or tended to be weak. When TI was present, its onset latencies (38.0, SD 3.6 ms versus 34.7, SD 3.3 ms) and transcallosal latencies were prolonged (18.5, SD 3.8 ms versus 14.8, SD 3.2 ms), while its duration was normal. These abnormal excitatory and inhibitory effects of fTMS suggest a reduced susceptibility of cortical excitatory and inhibitory neuronal structures compatible with a loss of neurons or a rarefication of their dendrites. Received: 1 December 1997 Received in revised form: 13 March 1998 Accepted: 27 April 1998     

Demyelination and axonal degeneration in corpus callosum assessed by analysis of transcallosally mediated inhibition in multiple sclerosis.

OBJECTIVE: Following focal transcranial magnetic cortex stimulation (fTMS), inhibition of voluntary EMG activity in the ipsilateral first dorsal interosseus (FDI) muscle was studied, in order to assess the functional integrity of the corpus callosum in patients with multiple sclerosis (MS). METHODS AND RESULTS: Thirty-four patients suffering from definite MS and 12 healthy, age-matched normal subjects were examined. In mid-sagittal slices, 29 patients showed lesions within the truncus corporis callosi in T2-weighted MRI. In 20 patients, all areas (anterior, middle and posterior parts), in one both the anterior and posterior part, in 3 exclusively the anterior, in 4 the middle and in one the posterior area were affected. In 5 patients, lesions of corpus callosum were lacking. In normal subjects, fTMS elicited a transient inhibition (TI) of preactivated (50% of maximal force) isometric voluntary ipsilateral FDI muscle activity. Mean onset latencies of TI were 35.5+/-5.4 ms in right and 36.1+/-4.2 ms in left FDI. Mean duration of TI amounted to 23.0+/-8.4 ms for right and 24.6+/-8.4 ms for left FDI. In the MS group, TI latencies were significantly increased in 23 and TI durations in 16 cases, whereas a lack of TI was found in 5 patients bilaterally and in 6 unilaterally. In patients, mean onset latencies of TI were 40.4+/-13.8 ms in right and 43.3+/-14.4 ms in left FDI, TI duration amounted to 30.5+/-17.4 ms for right and 31.0+/-25.2 ms for left FDI. Increase of onset latencies and durations of TI were positively correlated with the summed area of lesions of corpus callosum in representative mid-sagittal MRI slices. Significant correlations between TI onset latencies and duration on the one hand, and central motor conduction latencies along corticospinal tracts (CML) on the other hand, were not found. CONCLUSION: The present investigation indicates that measurement of TI elicited by fTMS seems to be a sensitive method for an assessment of demyelination and axonal degeneration within corpus callosum in MS patients.     

MEP latency shift after implantation of deep brain stimulation systems in the subthalamic nucleus in patients with advanced Parkinson's disease.

Deep brain stimulation (DBS) into the subthalamic nucleus (STN) is a highly effective treatment for advanced Parkinson's disease (PD). The consequences of STN stimulation on intracortical and corticospinal excitability have been addressed in a few studies using transcranial magnetic stimulation (TMS). Although excitability measurements were compared between the STN stimulation OFF and ON condition, in these experiments, there are no longitudinal studies examining the impact of electrode implantation per se on motor excitability. Here, we explored the effects of STN electrode implantation on resting motor thresholds (RMT), motor evoked potential (MEP) recruitment curves, and MEP onset latencies on 2 consecutive days before and shortly after STN surgery with the stimulator switched off, thus avoiding the effects of chronic DBS on the motor system, in 8 PD patients not taking any dopaminergic medication. After surgery, RMT and MEP recruitment curves were unchanged. In contrast, MEP onset latencies were significantly shorter when examined in relaxed muscles but were unchanged under preactivation. We hypothesize that postoperatively TMS pulses induced small currents in scalp leads underneath the TMS coil connecting the external stimulator with STN electrodes leading to inadvertent stimulation of fast-conducting descending neural elements in the vicinity of the STN, thereby producing submotor threshold descending volleys. These "conditioning" volleys probably preactivated spinal motor neurons leading to earlier suprathreshold activation by the multiple corticospinal volleys produced by TMS of the motor cortex. These TMS effects need to be considered when interpreting results of excitability measurements in PD patients after implantation of STN electrodes.     

Concurrent excitation of the opposite motor cortex during transcranial magnetic stimulation to activate the abdominal muscles

The study investigated the potential for stimulation of both motor cortices during transcranial magnetic stimulation (TMS) to evoke abdominal muscle responses. Electromyographic activity (EMG) of transversus abdominis (TrA) was recorded bilaterally in eleven healthy volunteers using fine-wire electrodes. TMS at 120% motor threshold (MT) was delivered at rest and during 10% activation at 1 cm intervals from the midline to 5 cm lateral, along a line 2 cm anterior to the vertex. The optimal site to evoke responses in TrA is located 2 cm lateral to the vertex. When bilateral abdominal responses were evoked at or lateral to this site, onset of ipsilateral motor evoked potentials (MEPs) were 3–4 ms longer than contralateral MEPs. The difference between latencies is consistent with activation of faster crossed-, and slower uncrossed-corticospinal pathways from one hemisphere. However, latencies of MEPs were similar between sides when stimulation was applied more medially and were consistent with concurrent activation of crossed corticospinal tracts on both sides. The findings suggest that stimulation of both motor cortices is possible when TMS is delivered less than 2 cm from midline. Concurrent stimulation of both motor cortices can be minimised if TMS is delivered at least 2 cm lateral to midline.     

Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke.

BACKGROUND AND PURPOSE: Recent research has shown that following stroke patients can display ipsilateral activity reflecting a functional link between the undamaged hemisphere and the affected upper limb on the same side of the body. In the present study the capacity for ipsilateral activation is documented during recovery by using transcranial magnetic stimulation (TMS) and transcranial Doppler (TCD). METHODS: Fourteen patients affected by hemispheric stroke were examined with TMS and TCD within 48 h of onset, and again 6 months later. Neurological signs were scored with reference to the NIHSS, and patients executed a thumb to finger opposition task so as to further estimate the motor deficit. Twenty healthy volunteers represented the control population. RESULTS: (1) Both TMS and TCD yielded homogeneous results showing ipsilateral activity between affected hands and undamaged hemispheres. On stimulating the motor cortex 3 cm anterior and 3 cm lateral to Cz, a scalp site remote from the primary motor area, ipsilateral motor evoked potentials (iMEPs) from hand muscles were found in recovered patients. (2) In 8 controls iMEPs with smaller amplitudes than patients could be obtained by stimulating only the left hemisphere. (3) TCD revealed increased blood flow velocity in the ipsilateral MCA by activating the recovering hand (10.5+/-3.3%; P<0.001). CONCLUSION: TMS reveals a specific area in the motor cortex from which ipsilateral MEPs can be elicited and both TMS and TCD indicate that an ipsilateral corticospinal tract can be accessible in some adult controls or becomes unmasked after cerebral damage.     

Callosal and corticospinal tract function in patients with hydrocephalus: a morphometric and transcranial magnetic stimulation study

In 15 patients with symptomatic hydrocephalus, pressure-induced morphological changes of the brain and the function of callosal and corticospinal fibres were studied. Morphometry of the corpus callosum (CC) was performed on midsagittal MR images. Focal transcranial magnetic stimulation of the motor cortex was used to assess simultaneously excitatory motor responses in contralateral hand muscle (corticospinally mediated effect) and inhibition of tonic EMG activity in ipsilateral hand muscles (transcallosal inhibition (TI) of the contralateral motor cortex). Before a shunt operation, the midsagittal area of the CC was reduced by 34% on average. The height and, to a lesser degree the length, of the CC were increased before the shunt operation. Thresholds and central motor latencies of corticospinally mediated responses were normal, response amplitudes were smaller than in normal subjects. Motor thresholds increased from 38, SD 5 to 52, SD 8% (P<0.01) within 7 days after ventricular drainage, reflecting the increase in the distance between stimulation coil and brain. The threshold increase paralleled a restoration of normal anatomical conditions within 7 days after shunt operation and the improvement of motor symptoms and might be a predictor of successful decompression. Transcallosal inhibition could be elicited in all patients. The measurements of TI lay within the normal range except the duration, which was prolonged in 73% of 15 patients before shunt operation as a probable indicator of an increased dispersion of callosal conduction. The normalization of the area and shape of the CC after shunt operation and the normal corticospinal and callosal conduction times exclude degeneration, demyelination or functional block of a large proportion of callosal or corticospinal tract fibres or a substantial loss of nerve cells in motor cortex. Received: 22 October 1997 Received in revised form: 13 January 1998 Accepted: 17 January 1998     

Tongue motor responses following transcranial magnetic stimulation of the motor cortex and proximal hypoglossal nerve in man

Surface recordings of EMG responses were performed bilaterally from the tongue following transcranial magnetic cortex (TCS) and nerve stimulation (TNS) to characterize the activated corticonuclear pathways and to obtain normative data for a diagnostic use. TCS over the face-associated motor cortex with 1.3 times the response threshold for relaxed muscles produced bilateral tongue responses with similar latencies and amplitudes for ipsi- (8.3±1.1 ms, 1.3±0.7 mV) and contralateral responses (8.5±1.0 ms, 1.7±0.8 mV, n=20, 10 subjects). In individual subjects maximal ipsilateral and contralateral responses were elicited by stimulation over about the same cortex area which lay 2–4 cm lateral and 0–2 cm anterior to the center of the hand motor representation area. Magnetic stimulation of the hypoglossal nerve with 70% of the maximal stimulator output and a circular coil placed over the posterior lateral skull produced a more proximal nerve excitation than electrical stimulation at the mandible, as reflected by the response latencies (3.4±0.9 ms vs. 2.1±0.7 ms). The effect of magnetic TNS was independent of the direction of the coil currents. Central motor latencies as calculated by subtracting the response latencies after TNS from the overall latency after TCS were 4.8±1.2 ms and 5.0±1.1 ms for ipsi- and contralateral responses, respectively. The findings suggest the existence of a direct and fast conducting connection between motor cortex and brainstem tongue motor nuclei on both sides in man.     

Long-term reorganization of motor cortex outputs after arm amputation.

OBJECTIVE: To investigate the reorganization of the corticospinal system long after arm amputation at different levels. METHODS: Focal transcranial magnetic stimulation (TMS) was performed in 15 patients 21 to 65 years after arm amputation at the level of the forearm, upper arm, or shoulder. Cortically elicited electromyographic responses were investigated in muscles immediately proximal to the stump. TMS was performed on a skull surface grid overlying the motor cortex. The response threshold, number of effective stimulation sites, and the sum of the amplitudes elicited at these sites were evaluated for slightly contracted muscles. RESULTS: Seven of eight patients with forearm amputation had larger stimulation effects in the biceps supplied by the motor cortex contralateral to amputation, as indicated by variable patterns of lowered response thresholds, increased response amplitudes, or increased numbers of effective stimulation sites. In seven patients with a more proximal amputation, the motor responses were investigated in the deltoid and trapezoid muscle. In only two of them, the motor cortex contralateral to amputation showed an increased excitability. Three patients presented with a higher excitability of the motor cortex contralateral to the intact arm and two with a balanced type of excitability. CONCLUSION: Reorganization of the motor system can be present more than 20 years after amputation. Furthermore, differential patterns of reorganized corticospinal output were found for different stump muscles, which might be due to varying amounts of ipsilateral corticospinal projections.     

Conduction deficits of callosal fibres in early multiple sclerosis

OBJECTIVE: To study the diagnostic usefulness of transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) in detecting central conduction deficits in early multiple sclerosis. Corticospinally mediated excitatory responses evoked by TMS are accepted as a sensitive diagnostic tool in multiple sclerosis. Recently, TI evoked by TMS has been introduced as a new paradigm to test the function of callosal fibres interconnecting both hand associated motor cortices. METHODS: Focal TMS of the motor cortex was performed in 50 patients with early relapsing-remitting multiple sclerosis. Corticospinally mediated (central motor latencies, amplitudes) and transcallosally mediated (onset latency and duration of TI) stimulation effects were investigated. RESULTS: TMS disclosed abnormalities of corticospinally mediated responses in 62% and of TI in 80% of the patients. CONCLUSION: The assessment of TI allows the discovery of lesions within the periventricular white matter that were not accessible by neurophysiological techniques before. This new paradigm increases the sensitivity of TMS with which to detect central conduction deficits in early multiple sclerosis.     

Residual function in motor cortex contralateral to amputated hand

OBJECTIVE: To investigate residual function of the motor cortex corresponding to the hand of the amputated arm (MCamp). METHODS: Focal transcranial magnetic stimulation (TMS) of MCamp was performed in 10 patients 22 to 52 years after arm amputation to inhibit tonic muscle contraction in the intact hand ipsilateral to cortex stimulation. RESULTS: In all patients, onset latency, degree, and duration of this inhibition were normal. CONCLUSION: The presence of motor inhibition in the residual hand of amputees originating from the hand motor representation of MCamp indicates residual cortical motor representation of the lost hand irrespective of whether the effect is mediated by commissural or ipsilateral corticospinal connections.     

Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Deep brain stimulation (DBS) implanted in different basal ganglia nuclei regulates the dysfunctional neuronal circuits and improves symptoms in movement disorders. However, the understanding of the neurophysiological mechanism of DBS is at an early stage. Transcranial magnetic stimulation (TMS) can be used safely in movement disorder patients with DBS, and can shed light on how DBS works. DBS at a therapeutic setting normalizes the abnormal motor cortical excitability measured with motor evoked potentials (MEP) produced by primary motor cortical TMS. Abnormal intracortical circuits in the motor cortex tested with paired-pulse TMS paradigm also show normalization with DBS. These changes are accompanied with improvements in symptoms after chronic DBS. Single-pulse DBS produces cortical evoked potentials recorded by electroencephalography at specific latencies and modulates motor cortical excitability at certain time intervals measured with MEP. Combination of basal ganglia DBS with motor cortical TMS at stimulus intervals consistent with the latency of cortical evoked potentials delivered in a repetitive mode produces plastic changes in the primary motor cortex. TMS can be used to examine the effects of open and closed loop DBS. Patterned DBS and TMS delivered in a repetitive mode may be developed as a new therapeutic method for movement disorder patients.     

Correlates of disability in multiple sclerosis detected by transcranial magnetic stimulation

OBJECTIVE: To study the usefulness of corticospinally mediated excitatory responses and transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) as a surrogate marker of disability in patients with different courses of MS. METHODS: Focal TMS of the motor cortex was performed in 118 patients with MS (96 with relapsing-remitting, 19 with primary progressive, and three with secondary progressive disease) who had an Expanded Disability Status Scale (EDSS) score between 0 and 6.5 and in 35 normal subjects. Central motor latencies (CML) and TI (onset latency, duration) were investigated. The Spearman rank correlation was used for statistical analysis. RESULTS: TMS disclosed prolonged CML in 52.5% and abnormal TI in 61% of the patients. In all patients the EDSS correlated with the frequency of abnormal TI (r = 0.58, p < 0.01) and abnormal CML (r = 0.51, p < 0.01). In patients with primary progressive MS (EDSS 1.5 to 6.5) the frequency of TI abnormalities correlated with EDSS (r = 0.65, p < 0.01) whereas CML did not. Delayed corticospinal responses in hand muscles always led to abnormal TI. CONCLUSIONS: The combination of central motor latencies and transcallosal inhibition evoked by transcranial magnetic stimulation yields objective data to estimate disease progression in MS as assessed by the EDSS.     

Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study.

OBJECTIVE: Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. METHODS: Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. RESULTS: TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. CONCLUSIONS: Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.     

Handedness is mainly associated with an asymmetry of corticospinal excitability and not of transcallosal inhibition.

OBJECTIVE: The study aims to compare transcallosal inhibition (TI), as assessed by the paired-pulse transcranial magnetic stimulation (TMS) technique, in a sample of right-handed subjects (RH) and left-handed subjects (LH). Motor thresholds (MTs) and motor evoked potential (MEP) amplitudes were also measured in the two groups, as an index of corticospinal activity. METHODS: Thirty-two normal subjects (16 RH and 16 LH) were recorded with a paired-pulse TMS paradigm (intensity of both pulses=120% of MT). The inter-stimulus intervals (ISIs) were 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 ms for both motor cortices, and MEP responses were recorded from the abductor digiti minimi muscles. RESULTS: Both groups showed a clear TI centred around the 12 ms ISI, but no difference was found as a function of handedness or of hemisphere. On the other hand, the two groups differed in terms of corticospinal activity, since the hand motor dominant hemisphere had lower MTs than the non-dominant one in LH, and larger MEP amplitudes for the right hand were found in RH. CONCLUSIONS: Results point to a functional asymmetry of the motor cortex on the hand-dominant versus the non-dominant hemisphere, while handedness does not seem associated with functional differences in callosal inhibition, as measured by the inter-hemispheric paired-pulse TMS technique.     

Inhibitory and facilitatory connectivity from ventral premotor to primary motor cortex in healthy humans at rest – A bifocal TMS study

ObjectiveIn macaques, intracortical electrical stimulation of ventral premotor cortex (PMv) can modulate ipsilateral primary motor cortex (M1) excitability at short interstimulus intervals (ISIs).MethodsAdopting the same conditioning-test approach, we used bifocal transcranial magnetic stimulation (TMS) to examine intrahemispheric connectivity between left PMv and M1 in humans. A conditioning stimulus (CS) was applied to PMv at intensities of 80% and 90% of active motor threshold (AMT) and 90% and 110% of resting motor threshold (RMT). A supra-threshold test stimulus (TS) was given 2, 4, 6, 8 and 10 ms after the CS and the amplitude of the motor evoked potential (MEP) was measured to probe corticospinal excitability.ResultsThe CS facilitated corticospinal excitability in ipsilateral M1 when PMv was stimulated with 80% AMT 4 or 6 ms before the TS. At the same ISIs, the CS suppressed corticospinal excitability when the stimulus intensity was increased to 90% RMT. Conditioning effects were site-specific because conditioning the dorsal premotor cortex (PMd) at three different sites produced different effects. Using neuronavigated TMS the PMv site where applied CS produced changes in ipsilateral M1 excitability was located at the border between ventral Brodmann area (BA) 6 and BA 44, the human homologue of monkey’s PMv (area F5).ConclusionWe infer that the corticospinal motor output from M1 to contralateral hand muscles can be facilitated or inhibited by a CS over ipsilateral PMv.SignificanceThe fact that conditioning effects following PMd stimulation differ from those after PMv stimulation supports the concept that inputs from premotor cortices to M1 are functionally segregated.     

Event-related desynchronization and excitability of the ipsilateral motor cortex during simple self-paced finger movements.

OBJECTIVE: To study the time course of oscillatory EEG activity and corticospinal excitability of the ipsilateral primary motor cortex (iM1) during self-paced phasic extension movements of fingers II-V. METHODS: We designed an experiment in which cortical activation, measured by spectral-power analysis of 28-channel EEG, and cortical excitability, measured by transcranial magnetic stimulation (TMS), were assessed during phasic self-paced extensions of the right fingers II-V in 28 right-handed subjects. TMS was delivered to iM1 0-1500 ms after movement onset. RESULTS: Ipsilateral event-related desynchronization (ERD) during finger movement was paralleled by increased cortical excitability of iM1 from 0-200 ms after movement onset and by increased intracortical facilitation (ICF) without changes in intracortical inhibition (ICI) or peripheral measures (F waves). TMS during periods of post-movement event-related synchronization (ERS) revealed no significant changes in cortical excitability in iM1. CONCLUSIONS: Our findings indicate that motor cortical ERD ipsilateral to the movement is associated with increased corticospinal excitability, while ERS is coupled with its removal. These data are compatible with the concept that iM1 contributes actively to motor control. No evidence for inhibitory modulation of iM1 was detected in association with self-paced phasic finger movements. SIGNIFICANCE: Understanding the physiological role of iM1 in motor control.     

Modulation of single motor unit discharges using magnetic stimulation of the motor cortex in incomplete spinal cord injury

OBJECTIVES: Motor evoked potentials (MEPs) and inhibition of voluntary contraction to transcranial magnetic stimulation (TMS) of the motor cortex have longer latencies than normal in patients with incomplete spinal cord injury (iSCI) when assessed using surface EMG. This study now examines the modulation of single motor unit discharges to TMS with the aim of improving resolution of the excitatory and inhibitory responses seen previously in surface EMG recordings. METHODS: A group of five patients with iSCI (motor level C4-C7) was compared with a group of five healthy control subjects. Single motor unit discharges were recorded with concentric needle electrodes from the first dorsal interosseus muscle during weak voluntary contraction (2%-5% maximum). TMS was applied with a 9 cm circular stimulating coil centred over the vertex. Modulation of single motor unit discharges was assessed using peristimulus time histograms (PSTHs). RESULTS: Mean (SEM) threshold (expressed as percentage of maximum stimulator output (%MSO)) for the excitatory peak (excitation) or inhibitory trough (inhibition) in the PSTHs was higher (p<0.05) in the patients (excitation = 47.1 (5.9) %MSO; inhibition = 44.3 (3.2) %MSO) than in controls (excitation=31.6 (1.2) %MSO; inhibition = 27.4 (1.0) %MSO). Mean latencies of excitation and inhibition were longer (p<0.05) in the patients (excitation=35 (1.8) ms; inhibition = 47.1 (1.8) ms) than in the controls (excitation = 21.1 (1.6) ms; inhibition = 27 (0.4) ms). Furthermore, the latency difference (inhibition-excitation) was longer (p<0.05) in the patients (10.4 (2.1) ms) than in the controls (6.2 (0.6) ms). CONCLUSION: Increased thresholds and latencies of excitation and inhibition may reflect degraded corticospinal transmission in the spinal cord. However, the relatively greater increase in the latency of inhibition compared with excitation in the patients with iSCI may reflect a weak or absent early component of cortical inhibition. Such a change in cortical inhibition may relate to the restoration of useful motor function after iSCI.     

Corticospinal tract development and its plasticity after perinatal injury

The final pattern of the origin and termination of the corticospinal tract is shaped during development by the balance between projection and withdrawal of axons. In animals, unilateral inhibition of the sensorimotor cortex during development results in a sparse contralateral projection from this cortex and retention of a greater number of ipsilateral projections from the more active cortex. Similarly in subjects with hemiplegic cerebral palsy if transcranial magnetic stimulation (TMS) of the damaged motor cortex fails to evoke responses in the paretic upper limb, TMS of the undamaged ipsilateral motor cortex evokes abnormally large and short-onset responses. Rather than representing a “reparative plasticity in response to injury”, this review presents evidence that increased ipsilateral projections from the non-infarcted motor cortex arise from perturbation of ongoing developmental processes, whereby reduced activity in the damaged hemipshere, leads to increased withdrawal of its surviving contralateral corticospinal projections because their terminals have been displaced by the more active ipsilateral projections of the undamaged hemisphere and thereby adding to the degree of long-term motor impairment.     

Characteristics of the human contra- versus ipsilateral SII cortex.

OBJECTIVES: In order to study the interaction between left- and right-sided stimuli on the activation of cortical somatosensory areas, we recorded somatosensory evoked magnetic fields (SEFs) from 8 healthy subjects with a 122 channel whole-scalp SQUID gradiometer. METHODS: Right and left median nerves were stimulated either alternately within the same run, with interstimulus intervals (ISIs) of 1.5 and 3 s, or separately in different runs with a 3 s ISI. In all conditions 4 cortical source areas were activated: the contralateral primary somatosensory cortex (SI), the contra- and ipsilateral secondary somatosensory cortices (SII) and the contralateral posterior parietal cortex (PPC). RESULTS: The earliest activity starting at 20 ms was generated solely in the SI cortex, whereas longer-latency activity was detected from all 4 source areas. The mean peak latencies for SII responses were 86-96 ms for contralateral and 94-97 ms for ipsilateral stimuli. However, the activation of right and left SII areas started at 61+/-3 and 62+/-3 ms to contralateral stimuli and at 66+/-2 and 63+/-2 ms to ipsilateral stimuli, suggesting a simultaneous commencing of activation of the SII areas. PPC sources were activated between 70 and 110 ms in different subjects. The 1.5 s ISI alternating stimuli elicited smaller SII responses than the 3 s ISI non-alternating stimuli, suggesting that a considerable part of the neural population in SII responds both to contra- and ipsilateral stimuli. The earliest SI responses did not differ between the two conditions. There were no significant differences in source locations of SII responses to ipsi- and contralateral stimuli in either hemisphere. Subaverages of the responses in sets of 30 responses revealed that amplitudes of the SII responses gradually attenuated during repetitive stimulation, whereas the amplitudes of the SI responses were not changed. CONCLUSIONS: The present results implicate that ipsi- and contralateral SII receive simultaneous input, and that a large part of SII neurons responds both to contra- and ipsilateral stimulation. The present data also highlight the different behavior of SI and SII cortices to repetitive stimuli.