Nick J. Davey

Facilitation of human first dorsal interosseous muscle responses to transcranial magnetic stimulation during voluntary contraction of the contralateral homonymous muscle

The size of compound motor evoked potentials (cMEPs) to transcranial magnetic stimulation of the motor cortex was measured in the relaxed first dorsal interosseous muscle of the nondominant hand (ndFDI) during different levels of voluntary contraction in the homonymous muscle of the dominant hand (dFDI). cMEP responses in the ndFDI became larger when the dFDI was contracted to forces ranging 10–70% of maximum voluntary contraction. Variability in the amplitude of the cMEP responses in ndFDI decreased when dFDI was contracted. Comparison with cMEPs to spinal cord stimulation suggested a large component of the facilitation was occurring at a cortical level. The amplitude of cMEP responses in ndFDI also increased when the tibialis anterior muscle of the leg on the contralateral side was contracted. The observed facilitation of motoneurons during contraction of contralateral muscles might involve a transcallosal pathway modulating the excitability of one cortex when the other is activated.

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.

Corticospinal excitability in patients with chronic low back pain.

Objective: This study was designed to investigate corticospinal excitability of lumbar muscles using transcranial magnetic stimulation (TMS) in patients with chronic low back pain and correlate this with self-rated measures of disability and pain. Methods: Twenty-four patients with chronic low back pain and 11 healthy control subjects were used in this study. TMS was delivered through an angled double-cone coil, with its cross-over on the vertex and a posterior-to-anterior current flow in the brain. Electromyographic (EMG) recordings were made from erector spinae (ES) muscles at the fourth lumbar level. Motor cortical excitability was assessed using motor threshold (MTh) for motor evoked potentials (MEPs) and threshold for silent period (SP) during facilitation of the back muscles. Latency, duration, and area of MEPs and SPs were also measured. Results: The latency, duration, and size of MEPs and SPs did not differ between the left and right ES muscles in either the patients or the control subjects and also did not differ between the patients and the control subjects. However, there was a significantly higher MTh and threshold for the SP in the patients as compared with the control subjects; the full significance of this requires further investigation. Interestingly, there was a positive correlation between the self-rated measure of disability (the Oswestry Disability Index score) and both the MTh and the threshold for the SP in the patients. There was also a positive correlation between the self-rated index of back pain and the threshold for the SP in the patients. This finding of an association between clinical and neurophysiologic measures reinforces the need for further research to establish the clinical relevance of these rises in MTh and SP threshold. Conclusions: In summary, this study has revealed that corticospinal excitability, driving ES muscles close to the site of pain, is lowered in patients with chronic low back pain.

Towards improved clinical and physiological assessments of recovery in spinal cord injury: a clinical initiative

Clinical practice and scientific research may soon lead to treatments designed to repair spinal cord injury. Repair is likely to be partial in the first trials, extending only one or two segments below the original injury. Furthermore, treatments that are becoming available are likely to be applied to the thoracic spinal cord to minimise loss of function resulting from damage to surviving connections. These provisos have prompted research into the improvement of clinical and physiological tests designed (1) to determine the level and density of a spinal cord injury, (2) to provide reliable monitoring of recovery over one or two spinal cord segments, and (3) to provide indices of function provided by thoracic spinal root innervation, presently largely ignored in assessment of spinal cord injury. This article reviews progress of the Clinical Initiative, sponsored by the International Spinal Research Trust, to advance the clinical and physiological tests of sensory, motor and autonomic function needed to achieve these aims.

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

Abstract 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.

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.

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. Spinal Cord (2000) 38, 292–300.

Relative increase in choline in the occipital cortex in chronic fatigue syndrome

Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002: 106: 224–226.

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.

Somatotopy of Perceptual Threshold to Cutaneous Electrical Stimulation in Man

Neurological testing tools for measuring and monitoring somatosensory function lack resolution and are often dependent on the clinician testing. In this study we have measured perceptual threshold (PT) to electrical stimulation of the skin and compared it with two‐point discriminative ability (TPDA) in 12 control subjects. Tests were made on both sides of the body at American Spinal Injury Association (ASIA) key points on seven spinal dermatomes (C3 (neck), C4 (shoulder), C5 (upper arm), C6 (thumb), T8 (abdomen), L3 (knee), L5 (foot)) and in the mandibular (chin) and maxillary (cheek) fields of the trigeminal (V) nerve. Electrical stimulation (0.5 ms pulse width; 3 Hz) was applied via a self‐adhesive cathode and an anode strapped to the wrist or ankle. The stimulus intensity was adjusted and PT was recorded as the lowest current at which the subject reported sensation. Sites were tested in random order. Indices for both TPDA and PT differed according to the dermatome tested but there was no correlation between TPDA and PT for any dermatome. There was good correlation between results from equivalent dermatomes on left and right sides for both PT and TPDA. Women frequently had lower mean (± s.e.) PTs and better TPDA than men; differences were significant (P < 0.05) for PT on the knee (women, 1.31 ± 0.15 mA; men, 2.05 ± 0.26 mA) and the foot (women, 2.90 ± 0.19 mA; men, 4.13 ± 0.28 mA) and for TPDA on the thumb (women, 3.8 ± 0.2 mm; men, 7.8 ± 1.3 mm) and the knee (women, 17.8 ± 1.6 mm; men, 27.1 ± 4.0 mm). Four subjects repeated the experiment on another day and the results correlated well with the first test for PT (r2, 0.62) and TPDA (r2, 0.48). PT differs between dermatomes in a predictable way but does not relate to TPDA. PT is easy to measure and may be a useful assessment tool with which to monitor recovery or deterioration in neuropathies, neurotrauma or after surgery.