Mapping the cortical representation of the lumbar paravertebral muscles.

OBJECTIVE: The aim of this study was to map the cortical representation of the lumbar spine paravertebral (LP) muscles in healthy subjects. METHODS: Transcranial magnetic stimulation (TMS) was employed to map the cortical representations of the LP muscles at two sites. Stimuli were applied to points on a grid representing scalp positions. The amplitude of motor evoked potentials (n=6) was averaged for each position. RESULTS: The optimal site for evoking responses in the contralateral LP muscles was situated 1cm anterior and 4 cm lateral to the vertex. Ipsilateral responses were evoked from sites lateral to the optimal site for evoking contralateral responses. Contralateral responses were also obtained from areas anterior to the optimal site. CONCLUSIONS: Maps of these muscles can be produced. The results suggest discrete contra- and ipsilateral cortical projections. Anterior sites at which excitation can be evoked may indicate projections arising in the SMA are involved. SIGNIFICANCE: This study provides normative data regarding the cortical representation of the paravertebral muscles and provides a technique for evaluating cortical motor plasticity in patients presenting with spinal pathologies.

Corticospinal function studied over time following incomplete spinal cord injury.

STUDY DESIGN: Longitudinal. OBJECTIVES: (1) To perform standard clinical neurological examinations and establish the pattern of clinical change with time following incomplete spinal cord injury (iSCI). (2) To establish the pattern of change in corticospinal electrophysiological function with time after iSCI. (3) To correlate clinical with electrophysiological findings. SETTING: The National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, UK and Imperial College School of Medicine, Charing Cross Hospital, London, UK. METHODS: Neurological assessments and classification were performed according to American Spinal Injuries Association and International Medical Society of Paraplegia (ASIA/IMSOP) standards. Twenty-one patients (ages 18 - 72 years) with iSCI (level C2 - C7, ASIA impairment grades C - D) and 10 healthy control subjects (ages 27 - 57 years) were studied. Electrophysiological tests of corticospinal function were carried out using transcranial magnetic stimulation (TMS) of the motor cortex and electromyographic (EMG) recordings from thenar muscles. Both tests were performed on a number of occasions, beginning 19 - 384 days and ending 124 - 1109 days post-injury, and the group data were pooled into time epochs of 50 or 100 days post-injury for analysis. Seven of the patients were studied on seven or more occasions and were also assessed individually. RESULTS: Individual and pooled data indicated that neurological scores improved progressively and tended to stabilise by around 300 days post-injury. When the patients were first assessed, the mean latency for motor evoked potentials (MEPs) and inhibition of voluntary EMG were significantly different from control values. There was no significant change in latency on subsequent sessions for either the grouped or individual patient data. There was no correlation between clinical assessment and electrophysiological data. CONCLUSION: We conclude that the weakened inhibition seen following iSCI is established within a few days of the time of spinal cord trauma. We argue that reduced corticospinal inhibition may be a prerequisite for the recovery of useful motor function. SPONSORSHIP: The work was supported by a project grant from The Wellcome Trust.

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.

Motor unit discharge characteristics during voluntary contraction in patients with incomplete spinal cord injury.

Synchronisation of motor unit discharges is commonly seen in hand muscles of normal man but is absent following neurologically complete spinal cord injury and reduced after stroke. These findings support the notion that some corticospinal inputs to motoneurones are shared and contribute to the observed synchrony of discharge. In this study we have examined motor unit discharge in hand muscles below the level of an incomplete spinal cord injury in an attempt to relate strength of synchrony to the integrity of the corticospinal tract. Eight patients with incomplete spinal cord injury (neurological level C3-C7) and eight control subjects took part in the study. The patients had sustained injury 14-191 weeks prior to the recordings and had since regained good motor function in their hands. Two concentric needle electrodes were inserted into the first dorsal interosseus muscle which subjects were instructed to contract weakly so that potentials from individual motor units could be reliably identified on both recordings. Synchrony was detected by constructing cross-correlograms between the discharges of pairs of individual motor units. The amount of synchronous firing was determined from the magnitude of any peak in the cross-correlogram, as the probability above chance (XP) of one motor unit firing with respect to the other and vice versa. The degree of synchrony was lower (P < 0.05) in the patient group (mean XP 0.06) than in the control group (mean XP 0.09). The incidence of significant synchrony was lower in the patient group (41.8 %) than in the control group (92.9 %). The mean (+/- S.E.M.) frequency of motor unit discharge was slightly lower (P < 0.05) in patients (9.7 +/- 0.4 impulses s-1) than controls (10.8 +/- 0.5 impulses s-1). The mean width of synchrony peaks was narrower (P < 0.05) in patients (11.4 +/- 1.1 ms) than controls (13.2 +/- 0.6 ms). We conclude that the weaker synchrony of motor unit discharge in incomplete spinal cord injury may reflect permanent damage to some corticospinal axons.

Comparison of input-output patterns in the corticospinal system of normal subjects and incomplete spinal cord injured patients.

We have examined input-output patterns in the corticospinal system after incomplete spinal cord injury. The amplitude of the motor evoked potential (MEP) to transcranial magnetic stimulation (TMS) was used to study the patterns of recruitment, with increasing stimulus intensity, and facilitation, with increasing voluntary contraction, in thenar muscles of 12 patients with incomplete spinal cord injuries and 13 control subjects. The patients had all suffered spinal cord injury at a segmental level rostral to C8 and T1, the segments supplying innervation of thenar muscles. The patients showed a less pronounced increase in MEP amplitude with increasing strength of TMS compared with the controls. Specifically, at a stimulus strength of 120% threshold and above, the patients showed significantly smaller MEPs relative to the maximum ulnar nerve M-wave response than the controls. The patients also showed a less steep pattern of facilitation with voluntary drive. The MEP continued to increase up to 50% maximum voluntary contraction (MVC) whereas the controls reached a plateau around 10% MVC. The results indicate that the patients show modified corticospinal recruitment and facilitation of the motoneurone pool. We speculate that the function of the adapted corticospinal system after spinal cord injury might be to regulate and modulate drive to motoneurones originating from segmental and other descending inputs. We discuss how such a modified corticospinal system might be of functional benefit to the patients.

The human motor cortex after incomplete spinal cord injury: an investigation using proton magnetic resonance spectroscopy.

OBJECTIVES: (1) A biochemical investigation of the motor cortex in patients with incomplete spinal cord injury and normal control subjects using proton magnetic resonance spectroscopy (MRS). (2) To relate any altered biochemistry with the physiological changes in corticospinal function seen after spinal cord injury. METHODS: A group of six patients with incomplete spinal cord injury who showed good recovery of motor function were selected. The patients were compared with five healthy control subjects. Electromyographic (EMG) responses of thenar muscles to transcranial magnetic stimulation (TMS) of the motor cortex showed that inhibition of cortical output was weaker in the patients than the controls. Proton MRS data were collected from a plane at the level of the centrum semiovale. Two 4.5 cm3 voxels in the motor cortex and a third voxel in the ipsilateral occipital cortex were examined in the patients and control subjects. RESULTS: The mean level of N-acetylaspartate (NAA), expressed relative to the creatine (Cr) peak (NAA/Cr), was significantly increased in the motor cortex of the patients compared with their ipsilateral occipital cortex or either cortical area in the controls. No differences between patients and controls were seen for any of the other metabolite peaks (choline (Cho), glutamate/glutamine (Glx) or the aspartate component of NAA (AspNAA)) relative to Cr. Choline relative to Cr (Cho/Cr) was higher in the motor cortex of the control subjects than in their ipsilateral occipital cortex. This difference was not present in the patients. CONCLUSIONS: Raised NAA/Cr in the motor cortex of the patients probably results from increased NAA rather than a decrease in the more stable Cr. The possible relevance of a raised NAA/Cr ratio is discussed, particularly with regard to the changed corticospinal physiology and the functional recovery seen in the patients.

Variability in the amplitude of skeletal muscle responses to magnetic stimulation of the motor cortex in man.

We have investigated variability in the amplitude of compound motor evoked potentials (cMEPs) in right and left thenar and wrist extensor muscles in response to synchronous bilateral transcranial magnetic stimulation (TMS) of the motor cortices using two figure-of-eight stimulating coils. Trials of 50 stimuli revealed a wide range of variability in cMEP amplitudes in relaxed muscles (coefficient of variation, range 0.22-1.12). The amplitudes of the cMEPs in one muscle correlated positively with those in the others. The r2 values (mean +/- SEM) were 0.27 +/- 0.06 for muscles on the same side of the body and 0.19 +/- 0.04 for muscles on opposite sides. Employing the ECG to trigger TMS, clamping the coil relative to the head or altering the orientation of the coil all failed to affect the variability of cMEPs. We conclude that fluctuations in excitability of the corticospinal pathway give rise to the variability in the response to TMS, that they are wide-ranging with respect to the muscles affected, and include a bilateral component. We argue that the variability reveals fluctuations in excitability mainly at the cortical rather than the spinal level. We suggest that measures of variability might provide an indication of cortical activity in conditions where consciousness and voluntary movement are compromised.

Responses of thenar muscles to transcranial magnetic stimulation of the motor cortex in patients with incomplete spinal cord injury.

OBJECTIVE: To investigate changes in electromyographic (EMG) responses to transcranial magnetic stimulation (TMS) of the motor cortex after incomplete spinal cord injury in humans. METHODS: A group of 10 patients with incomplete spinal cord injury (motor level C3-C8) was compared with a group of 10 healthy control subjects. Surface EMG recordings were made from the thenar muscles. TMS was applied with a 9 cm circular stimulating coil centred over the vertex. The EMG responses to up to 50 magnetic stimuli were rectified and averaged. RESULTS: Thresholds for compound motor evoked potentials (cMEPs) and suppression of voluntary contraction (SVC) elicited by TMS were higher (p < 0.05) in the patient group. Latency of cMEPs was longer (p < 0.05) in the patient group in both relaxed (controls 21.3 (SEM 0.5) ms; patients 27.7 (SEM 1.3) ms) and voluntarily contracted (controls 19.8 (SEM 0.5) ms; patients 27.6 (SEM 1.3) ms) muscles. The latency of SVC was longer (p < 0.05) in the patients (51.8 (SEM 1.8) ms) than in the controls (33.4 (SEM 1.9) ms). The latency difference (SVC-cMEP) was longer in the patients (25.3 (SEM 2.4) ms) than in the controls (13.4 (SEM 1.6) ms). CONCLUSION: The longer latency difference between cMEPs and SVC in the patients may reflect a weak or absent early component of cortical inhibition. Such a change may contribute to the restoration of useful motor function after incomplete spinal cord injury.

Facilitation of a hand muscle response to stimulation of the motor cortex preceding a simple reaction task.

Transcranial magnetic stimulation (TMS) of the motor cortex was used to produce compound motor evoked potentials (cMEPs) in the first dorsal interosseus (FDI) muscle. The size of cMEPs was measured as an index of corticospinal excitability before and after initiation of a simple reaction task (SRT). The SRT, consisting of an abduction of the right index finger against a vertical support in response to a 1 kHz cueing tone, was performed in 6 healthy male subjects. cMEPs were facilitated when timed to occur just before the fastest simple reaction time (fSRT). When the cMEP was placed 15.5 +/- 1.5 ms before the fSRT, its amplitude increased to 176 +/- 36% of the control response seen in the relaxed state (no SRTs). Facilitation of the cMEP increased to 382 +/- 43% of the control when it was placed 11.9 +/- 1.5 ms after the fSRT. The facilitation of cMEP responses prior to the SRT is discussed with particular reference to the premovement potential that may be recorded over the cortex prior to a voluntary movement.

Magnetic stimulation excites skeletal muscle via motor nerve axons in the cat.

Surface magnetic stimulation has been applied directly over skeletal muscle (triceps surae) in decerebrated cats. Recordings were made of the twitch contraction and electromyographic responses in triceps surae, and of the centripetal nerve volley in the sciatic nerve or spinal roots. Stimulus/response curves were established up to the maximum output of the magnetic stimulator. Neuromuscular blockade abolished the twitch contraction and muscle action potential leaving the nerve volley unaffected. Raising the stimulator output to its maximum increased the size of the nerve volley but failed to produce any muscle response. We conclude that magnetic stimulation applied directly to skeletal muscle excites via stimulation of motor nerve axons. The maximum output of the stimulator was incapable of exciting muscle fibers by direct depolarization. Use of magnetic stimulation in the clinical appraisal of muscle function should be interpreted in the knowledge that the stimulator elicits contraction only indirectly through nerve stimulation.

Site of facilitation of diaphragm EMG to corticospinal stimulation during inspiration.

The electromyographic response of the diaphragm to (a) transcutaneous electrical stimulation (TCES) of the spinal cord at C5 and above, (b) transcranial magnetic stimulation (TMS) over the motor cortex and (c) transcutaneous electrical stimulation of the phrenic nerve in the neck (TPNS), was recorded in six normal subjects at the antero-lateral chest wall. The compound motor evoked potentials (cMEPs) recorded in response to both TMS and TCES were facilitated to a similar extent during volitional inspiration; this facilitation was greater than any change seen in response to TPNS with inspiration. The results show that facilitation of the response in the diaphragm to TMS during volitional inspiration is due to increased excitability at synapses associated with the spinal motoneurone pool, but they do not exclude a component due to increased higher centre excitability. We conclude that it is unsafe to assign a cortical contribution to 'automatic' inspiration on the sole basis of facilitation of the electromyographic response in the diaphragm to TMS.

The relation between bradykinesia and excitability of the motor cortex assessed using transcranial magnetic stimulation in normal and parkinsonian subjects.

The response of single motor units in the first dorsal interosseus (FDI) muscle to transcranial magnetic stimulation (TMS) of the motor cortex has been assessed using the post-stimulus time histogram during weak voluntary contraction in patients with parkinsonian symptoms and in age-matched, normal subjects. Patients and subjects were required to maintain the discharge of a motor unit at a steady rate during TMS. Responses were evident in post-stimulus time histograms of motor unit discharges as single or double peaks at mean (+/- S.E.) latencies of 23.4 msec (+/- 0.7) for normal subjects and 24.9 msec (+/- 0.9) for parkinsonian patients. There were no significant differences in latency or tendency to double peaks in the responses of motor units when normal subjects and parkinsonian patients were compared. The group data showed no significant difference between the threshold TMS for modulation of the discharge of single motor units in patients and normal subjects. However, 7 of the 15 parkinsonian patients, but only 1 of 15 normal subjects, had thresholds to TMS greater than or equal to 45% of the maximum output of the magnetic stimulator. Speed of movement was measured by 3 tasks: (1) timed stand/walk/sit, (2) timed peg-board test, (3) frequency of 2-point table taps. In the parkinsonian group there was a positive linear correlation between threshold to TMS and degree of bradykinesia for each individual score and the average score on the tests of speed of movement. This was not evident for the normal group. The results are discussed in the light of current views on the mode of action of TMS. The findings are consistent with the conclusion that parkinsonian patients exhibiting pronounced bradykinesia have a lowered excitability of the motor cortex.

Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man.

1. Suppression of voluntary muscle activity of hand and arm muscles in response to transcranial magnetic stimulation (TMS) of the motor cortex has been investigated in man. 2. Suppression could be elicited by low levels of TMS without any prior excitatory response. The latency of the suppression was 3-8 ms longer than the excitation observed at a higher stimulus intensity. The duration of the suppression ranged from 8 to 26 ms. 3. A circular stimulating coil was used to determine threshold intensity for excitation and suppression of contraction of thenar muscles in response to TMS at different locations over the motor cortex. The locations for lowest threshold excitation coincided with those for lowest threshold suppression. Suppression was elicited at a lower threshold than excitation at all locations. 4. A figure-of-eight stimulating coil was positioned over the left motor cortex at the lowest threshold point for excitation of the right thenar muscles. The orientation for the lowest threshold excitatory and inhibitory responses was the same for all subjects. That orientation induced a stimulating current travelling in an antero-medial direction. Suppression was invariably elicited at lower thresholds than excitation. 5. When antagonistic muscles (second and third dorsal interosseus) were co-contracted, TMS evoked coincident suppression of voluntary EMG in the two muscles without prior excitation of either muscle. This suggests that the suppression is not mediated via corticospinal activation of spinal interneurones. 6. Test responses to electrical stimulation of the cervical spinal cord were evoked in both relaxed and activated thenar muscles. In the relaxed muscle, prior TMS at an intensity that would suppress voluntary activity failed to influence the test responses, suggesting absence of inhibition at a spinal level. However, in the activated muscle, prior TMS could reduce the test response. This may be explained by disfacilitation of motoneurones due to inhibition of corticospinal output. 7. We propose that suppression of voluntary muscle activity by TMS is due in large part to activation of a mechanism within the motor cortex that reduces the corticospinal output to the muscle. It is concluded that TMS evokes excitation and inhibition via neuronal structures lying close to one another and having similar orientations.

Motor cortical representation of the diaphragm in man.

1. Transcranial magnetic stimulation was performed using a figure-of-eight-shaped coil over the right motor cortex with the aim of identifying those areas involved with activation of the diaphragm. 2. The response of the right and left hemi-diaphragms was recorded using surface electrodes in either the 7th or 8th intercostal spaces 3 cm lateral to the anterior costal margin on either side. 3. The compound muscle action potentials recorded over the left diaphragm in response to transcranial magnetic stimulation were maximal when the centre of the figure-of-eight coil was placed approximately 3 cm to the right of the mid-line and 2-3 cm anterior to the auricular plane. 4. The amplitude of the response recorded from the diaphragm depended upon the angulation of the figure-of-eight coil and hence the direction of the stimulating current. 5. The response of the inspiratory muscles to magnetic stimulation of one side of the brain was predominantly contralateral but a small response was seen on the ipsilateral side. Ultrasonic techniques confirmed that the diaphragm was responding contralaterally and not ipsilaterally.