Jan Däuper

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.

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.

Functional lesions and human action monitoring: combining repetitive transcranial magnetic stimulation and event-related brain potentials

OBJECTIVE Electrophysiological recordings of the error-related negativity (ERN) and functional imaging data point to an involvement of medial frontal cortex (including the anterior cingulate cortex, ACC) and dorsolateral prefrontal cortex (DLPFC) in the detection and correction of performance errors. Here, we studied this network by applying trains of rapid transcranial magnetic stimulation (rTMS) prior to the recording of the ERN. METHODS Low-frequency (0.9 Hz) rTMS was applied to medial frontal or lateral frontal regions (different sessions) for 60 s immediately before each 3 min ERN recording in 11 healthy young subjects. The ERN was obtained by multichannel recordings in a typical Eriksen flanker task with instructions calling for immediate error correction in case a performance error was detected by the subject. Event-related potentials were quantified and statistically evaluated using standard methodology. RESULTS Compared to a no-stimulation control condition, medial frontal stimulation led to a small but reliable decrease in the number of corrected errors as well as to an attenuation of the ERN and an increase of the subsequent error-positivity (Pe). No effect on these components was seen after lateral frontal stimulation. No reliable effects on the lateralized readiness potential were observed. CONCLUSIONS Functional lesions by rTMS appear to interfere with the functions of the medial frontal cortex in error detection and correction.

Impaired sensorimotor integration in cervical dystonia: a study using transcranial magnetic stimulation and muscle vibration.

Summary The authors studied the effects of sensorimotor integration (corticocortical inhibition and facilitation during muscle vibration [MV]) in dystonic patients. Eleven patients with cervical dystonia and 11 age-matched healthy control subjects were enrolled in the study. They were examined using transcranial magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse transcranial magnetic stimulation was done at interstimulus intervals of 3 msec (intracortical inhibition) and 13 msec, the intensity of the conditioning stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor evoked potentials were recorded from the vibrated extensor carpi radialis muscle and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz; amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients and healthy control subjects during MV only. Intracortical inhibition was pronounced significantly only in control subjects, whereas intracortical facilitation was significant in patients only (P < 0.05). Furthermore, the significant reduction of motor evoked potentials at 13-msec interstimulus intervals, which can be found in healthy subjects frequently, was observed in one dystonia patient only. The results of the current study suggest that sensorimotor integration is impaired in cervical dystonia, probably by an altered control of proprioceptive (vibratory) input.

Brain potentials index executive functions during random number generation.

The generation of random sequences is considered to tax different executive functions. To explore the involvement of these functions further, brain potentials were recorded in 16 healthy young adults while either engaging in random number generation (RNG) by pressing the number keys on a computer keyboard in a random sequence or in ordered number generation (ONG) necessitating key presses in the canonical order. Key presses were paced by an external auditory stimulus to yield either fast (1 press/800 ms) or slow (1 press/1300 ms) sequences in separate runs. Attentional demands of random and ordered tasks were assessed by the introduction of a secondary task (key-press to a target tone). The P3 amplitude to the target tone of this secondary task was reduced during RNG, reflecting the greater consumption of attentional resources during RNG. Moreover, RNG led to a left frontal negativity peaking 140 ms after the onset of the pacing stimulus, whenever the subjects produced a true random response. This negativity could be attributed to the left dorsolateral prefrontal cortex and was absent when numbers were repeated. This negativity was interpreted as an index for the inhibition of habitual responses. Finally, in response locked ERPs a negative component was apparent peaking about 50 ms after the key-press that was more prominent during RNG. Source localization suggested a medial frontal source. This effect was tentatively interpreted as a reflection of the greater monitoring demands during random sequence generation.

Decrease of middle cerebral artery blood flow velocity after low-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex

OBJECTIVES Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in a variety of neuropsychiatric disorders. Both, inhibition and activation of cortical areas may be achieved using different stimulation parameters. Using low-frequency rTMS (0.9 Hz), inhibition of cortical areas can be observed. METHODS In the present study, 38 right-handed, healthy, normotensive subjects (aged 21-50 years, mean 30.2 years, SD=4.9; 17 women) were enrolled. Twenty-five participants received active rTMS (5 min of 0.9 Hz rTMS, stimulus intensity 90% of motor threshold) of the right dorsolateral prefrontal cortex. Sham stimulation (n=13 subjects) occurred in the same manner as active rTMS, except that the angle of the coil was at 45 degrees off the skull. Simultaneously, ipsilateral and contralateral maximal middle cerebral artery (MCA) flow velocity (and pulsatility index, PI) was monitored using transcranial Doppler sonography. RESULTS In the group with active rTMS, maximal MCA flow velocity decreased from a baseline (before rTMS) of 101.6 cm/s (SD=26.0) to a mean of 92.6 cm/s (SD=23.7) immediately after rTMS, T=5.06, P<0.001. This equals a mean decrease of 9.0 cm/s (SD=8.3) or approximately 8.9% of baseline flow. Five and 10 min after rTMS, there was a return to baseline. PI significantly decreased 10 min after rTMS (mean difference -0.05, SD=0.05, T=2.29, P<0.05). In the contralateral MCA, maximal flow velocity tended to increase 10 min after rTMS (mean difference +7.4 cm/s, SD=17.5; T=-2.03, P=0.054). With sham rTMS, no significant changes occurred. CONCLUSIONS The results from our study support the hypothesis that low-frequency rTMS may influence cerebral blood flow (CBF) over short periods of time, inducing a temporary decrease of maximal CBF in the ipsilateral MCA followed by an increase in the contralateral MCA.

Changes in processing of proprioceptive information in Parkinson’s disease and multiple system atrophy

OBJECTIVE Changes in processing of proprioceptive information are known in idiopathic Parkinsons disease (IPD) and may contribute to motor deficits. This study used transcranial magnetic stimulation (TMS) to investigate the processing of proprioceptive information induced by muscle vibration (MV) in 10 patients with IPD and 10 patients with multiple system atrophy of the parkinsonian type (MSA-P) in comparison to 10 controls. METHODS Single and paired-pulses were used, and motor evoked potentials (MEPs) were recorded in the extensor and flexor carpi radialis muscles (ECR and FCR) without and with MV (80Hz) to the ECR. Cortical silent periods (SP) were also studied. RESULTS Controls showed the known MV-induced focal MEP augmentation which was lacking in IPD and intermediate and less focal in MSA-P. Intracortical inhibition and facilitation were not influenced by MV. SP was not changed by MV in controls and IPD while it was significantly prolonged in MSA-P. CONCLUSIONS Processing of proprioceptive information is differently changed in IPD and MSA-P. Cortical facilitation by MV is more impaired in IPD than MSA-P, and these changes are less focal in MSA-P than in controls. SIGNIFICANCE Our results support the view that changes in processing of proprioceptive information may contribute to motor deficits in patients with IPD and MSA-P.

Brain potentials and self-paced random number generation in humans

Random number generation (RNG) requires executive control. A novel paradigm using the eight drum pads of an electronic drum set as an input device was used to test 15 healthy subjects who engaged in random or ordered number generation (ONG). Brain potentials time-locked to the drum-beats revealed a more negative response during RNG compared to ONG which had a left frontal distribution. Source analysis pointed to Brodmann area 9, which has been reported previously in a PET study and is thought to be engaged in suppression of habitual responses such as counting up in steps of one during RNG. Lateralized readiness potentials reflecting the difference in activation of the contra and ipsilateral motor cortex were smaller during ONG reflecting the ability to preprogram such canonical sequences.

Chapter 39 Repetitive magnetic stimulation for the treatment of chronic pain conditions

Publisher Summary This chapter performs two studies to evaluate antalgic efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) administered to MI and peripheral repetitive magnetic stimulation (rMS) administered to the extensor carpi radialis muscle in chronic lateral epicondylitis patients. Invasive electrical motor cortex stimulation (MCS) may ameliorate symptoms in intractable chronic pain sufferers. It may be hypothesized that different treatment protocols have accounted for controversial results. Taken into account that MCS techniques employ a chronic stimulation, longer rTMS stimulation periods may be considered. Antalgic efficacy of rMS administered to the extensor carpi radialis muscle in chronic lateral epicondylitis patients has been examined. While the results of both studies defy ready summary, repetitive magnetic stimulation—both rTMS (applied to MI) and rMS (applied to the periphery)—failed to show any significant antalgic effects. Further studies are encouraged, employing larger sample sizes and using different stimulation techniques, to decide whether repetitive magnetic stimulation might useful in therapy-resistant chronic pain conditions.