Andon Kossev

Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Pain – A Pilot Study

Invasive electrical stimulation of the motor cortex has been reported to be of therapeutic value in pain control. We were interested whether noninvasive repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex might also act beneficially. Twelve patients with therapy-resistant chronic pain syndromes (mean age 51.3 ± 12.6, 6 males) were included in a pilot study. They were treated with rTMS of the corresponding motor cortex area for 20 min (20 Hz, 20 × 2 s trains, intensity 80% of motor threshold) and sham stimulation (sequence-controlled cross-over design). Some of the patients (6/6) had an analgesic effect, but for the whole group, the difference between active and sham stimulation did not reach a level of significance (active rTMS: mean VAS reduction –4.0 ± 15.6%; sham rTMS: –2.3 ± 8.8%). Further studies using different rTMS stimulation parameters (duration and frequency of rTMS) or stimulation sites (e.g. anterior cingulate gyrus) are strongly encouraged.

Discharge pattern of human motor units during dynamic concentric and eccentric contractions.

OBJECTIVES A total of 45 motor units (MUs) from the human biceps brachii muscle were investigated during isovelocity concentric and eccentric movements performed by means of a device implementing an external torque in the direction of the extension proportionally to the elbow angle changes. The effects of movement velocity on the recruitment and decruitment thresholds (RT and DT) and the corresponding discharge patterns were determined. METHODS A wire branched electrode placed subcutaneously was used to discriminate the potentials from a single MV. RESULTS The majority of MUs (91%) were recruited at lower torque values with the increase of movement velocity. The decrease of RT was statistically significant for 47% of the investigated MUs. A typical discharge pattern of short first interspike interval (ISI) followed by a longer one was observed for 93% of all MUs. After the first 2-3 spikes the rate of the MU discharge was approximately constant regardless of the fact that the muscle force gradually increased until the end of the concentric movement. CONCLUSIONS There are differences in the muscle force control during shortening and lengthening contractions. For 82% of the investigated MUs DT was smaller at faster movements and for 21 MUs (47%) the decrease of DT was significant. The gradually declined MU discharge rate throughout the entire movement with a very long last ISI was demonstrated for 93% of the investigated MUs.

Muscle vibration: Different effects on transcranial magnetic and electrical stimulation

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) were applied before and 3 s after onset of vibration (0.5 mm, 80 Hz) of the right extensor carpi radialis muscle in 5 healthy subjects. Vibration induced significant augmentation and latency shortening of motor evoked potentials elicited by TMS, but not TES. This provides evidence for an involvement of cortical mechanisms by muscle vibration in the augmentation of MEPs following TMS.

Increased intracortical inhibition in middle-aged humans; a study using paired-pulse transcranial magnetic stimulation

Using single and paired-pulse transcranial magnetic stimulation we compared the cortical excitability in two different age groups of healthy subjects (mean+/-SD age: 28.5+/-5.2 vs. 56.1+/-4.9 years). Motor evoked potentials were recorded from right extensor and flexor carpi radialis muscles. The effect of paired-pulse stimulation was assessed by the ratio conditioned/unconditioned response area with interstimulus intervals of 3 and 13 ms to test for intracortical inhibition and facilitation, respectively. To test the influence of sensory input the experiments were conducted without and with vibration of the extensor carpi radialis muscle. The intracortical inhibition was significantly greater in older subjects; however, during muscle vibration this difference between the two groups vanished. The different effect of vibration favors compensatory mechanisms to be responsible for a different paired-pulse excitability in middle-aged subjects.

Modulation of motor evoked potentials by muscle vibration: The role of vibration frequency

Augmentation of motor evoked potentials (MEPs) by muscle vibration (MV) was studied in 10 healthy subjects with regard to the vibration frequency (VF). The extensor carpi radialis muscle (ECR) was vibrated using VFs of 80, 120, and 160 Hz. Motor evoked potentials following transcranial magnetic stimulation were recorded simultaneously from the vibrated ECR and the antagonist flexor carpi radialis muscle (FCR) without MV, 0.5 s and 3 s after onset of MV and 1 s after offset. Only the VFs of 80 Hz and 120 Hz caused MEP augmentation and latency shortening in ECR, whereas depression of MEPs in FCR was induced by all VFs used. It appears that MEP augmentation and latency shortening in ECR are mediated by the primary muscle spindle endings which respond with optimal discharge rates to VFs of up to 100 Hz. Motor evoked potential depression in FCR, being well expressed also with VF 160 Hz, seems to involve other dynamic mechanoreceptors.

Effects of low‐frequency whole‐body vibration on motor‐evoked potentials in healthy men

The aim of this study was to determine whether low‐frequency whole‐body vibration (WBV) modulates the excitability of the corticospinal and intracortical pathways related to tibialis anterior (TA) muscle activity, thus contributing to the observed changes in neuromuscular function during and after WBV exercise. Motor‐evoked potentials (MEPs) elicited in response to transcranial magnetic stimulation (TMS) of the leg area of the motor cortex were recorded in TA and soleus (SOL) muscles of seven healthy male subjects whilst performing 330 s continuous static squat exercise. Each subject completed two conditions: control (no WBV) and WBV (30 Hz, 1.5 mm vibration applied from 111 to 220 s). Five single suprathreshold and five paired TMS were delivered during each squat period lasting 110 s (pre‐, during and post‐WBV). Two interstimulus intervals (ISIs) between the conditioning and the testing stimuli were employed in order to study the effects of WBV on short‐interval intracortical inhibition (SICI, ISI = 3 ms) and intracortical facilitation (ICF, ISI = 13 ms). During vibration relative to squat exercise alone, single‐pulse TMS provoked significantly higher TA MEP amplitude (56 ± 14%, P= 0.003) and total area (71 ± 19%, P= 0.04), and paired TMS with ISI = 13 ms provoked smaller MEP amplitude (−21 ± 4%, P= 0.01) but not in SOL. Paired‐pulse TMS with ISI = 3 ms elicited significantly lower MEP amplitude (TA, −19 ± 4%, P= 0.009; and SOL, −13 ± 4%, P= 0.03) and total area (SOL, −17 ± 6%, P= 0.02) during vibration relative to squat exercise alone in both muscles. Tibialis anterior MEP facilitation in response to single‐pulse TMS suggests that WBV increased corticospinal pathway excitability. Increased TA and SOL SICI and decreased TA ICF in response to paired‐pulse TMS during WBV indicate vibration‐induced alteration of the intracortical processes as well.

Triple stimulation technique (TST) in amyotrophic lateral sclerosis

OBJECTIVE The authors studied amyotrophic lateral sclerosis (ALS) patients using triple stimulation technique (TST) to detect upper motor neuron (UMN) involvement. METHODS Nineteen ALS patients (aged 45-72 years) were enrolled in the study. According to the El Escorial criteria, 6 diagnoses were suspected or possible, 6 probable, and 7 definite. Patients were examined clinically, with conventional (single-pulse) transcranial magnetic stimulation (TMS), and with TST (on one side only). RESULTS Among the whole group of patients, TST appeared to be more sensitive than conventional TMS techniques. In particular among suspected/possible ALS patients, TST area ratio was pathologic in 100%, while single-pulse TMS was abnormal only in 50% of cases. Overall, the use of TST area ratio was more sensitive than the analysis of TST amplitude ratio. CONCLUSIONS The results suggest that TST might be more sensitive and useful in the diagnosis of subclinical UMN involvement than conventional TMS techniques, even if TST is performed on one side only.

Crossed effects of muscle vibration on motor-evoked potentials

OBJECTIVES Muscle vibration (MV) to a forearm muscle augments motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and the underlying mechanism involves cortical structures. Although MV-induced cortical activation is bilateral, the effects of MV on MEPs in contralateral muscles have not been investigated. METHODS Low-amplitude MV (80 Hz, amplitude 0.5 mm, duration 4 s), subthreshold for the tonic vibration reflex, was applied to the right extensor carpi radialis muscle (ECR). MEPs were elicited (0.5, 3 and 5 s after MV onset) in the left and right ECR and flexor carpi radialis muscle (FCR) by TMS (120% of threshold at rest) to the left and right hemisphere, respectively. RESULTS During MV of right ECR the left ECR revealed a slight non-significant augmentation of MEPs. In contrast, the left FCR showed a gradual depression of MEPs with ongoing MV and at 3 s the reduction of MEPs was significant. The time course of MEP changes in left FCR correlated with the facilitation of the vibrated right ECR. Post-vibration MEPs at 1 s after the offset of MV were still significantly decreased. CONCLUSIONS The study demonstrates crossed effects of MV on motor cortex excitability, suggesting transcallosal MEP modulation.

Motor unit activity during long-lasting intermittent muscle contractions in humans

Abstract Changes accompanying long-lasting intermittent muscle contractions (30%–50% of the maximal) were investigated by tracing the activity of 38 motor units (MU) of the human biceps brachii muscle recorded from fine-wire branched electrodes. The motor task was a continuous repetition of ramp-and-hold cycles of isometric flexion contractions. During ramp-up phases a significant decline in recruitment thresholds was found with no changes in the discharge pattern. During ramp-down phases the unchanged mean value of derecruitment thresholds during the task was accompanied by increased duration of the last two interspike intervals (ISI). These findings would suggest that during fatigue development the main compensatory mechanism during ramp-up contractions is space coding while for ramp-down contractions it is rate coding. During the steady-state phases the mean value of ISI, as well as the firing variability, had increased by the end of the task in most of the MU investigated . In addition 17 recruited MU were also investigated. These units revealed a lower initial discharge rate and a faster decrease in the mean discharge rate with the development of fatigue. The gradual reduction of the recruitment threshold of already active MU and the recruitment of new units demonstrated an increased excitability of the motorneuron pool during fatigue. A typical recruitment pattern (a first short ISI followed by a long one) was observed during ramp-up contractions in units active from the very beginning of the task, as well as during sustained contractions at the onset of the stable discharge of the additionally recruited MU.

Discharge rate of selected motor units in human biceps brachii at different muscle lengths

Action potentials of selected motor units (MUs) from biceps brachii muscle were recorded and analysed at three different elbow angles: 90, 120 and 150 degrees, corresponding to short, control and long muscle length, respectively. Using branched and conventional bipolar wire electrodes, superficial and deep-situated MUs were selectively recorded at relatively equal torques (the torque values were normalized to the corresponding maximal torque for a given muscle length). A total of 138 MUs (74 superficial and 64 deep) were investigated. The mean interspike intervals were significantly shorter at 90 degrees for the majority (52.2%) of the investigated MUs than at the other two angles. This increased discharge rate compensates for the reduction of twitch duration of evoked contraction at short muscle length. The other MUs were divided into three almost equal groups: two with significantly higher discharge rates at 120 and 150 degrees and one with discharge rates unaffected by the joint angle. No significant difference in the discharge rate of superficial and deep MUs at a fixed joint angle was found.