High-frequency oscillations change in parallel with short-interval intracortical inhibition after theta burst magnetic stimulation.

OBJECTIVE: Theta burst transcranial magnetic stimulation (TBS) causes changes in motor cortical excitability. In the present study, somatosensory-evoked potentials (SEPs) and high-frequency oscillations (HFOs) were recorded before and after TBS over the motor cortex to examine how TBS influenced the somatosensory cortex. METHODS: SEPs following electric median nerve stimulation were recorded, and amplitudes for the P14, N20, P25, and N33 components were measured and analyzed. HFOs were separated by 400-800 Hz band-pass filtering, and root-mean-square amplitudes were calculated from onset to offset. SEPs and HFOs were measured before and after application of either intermittent or continuous TBS (iTBS/cTBS; 600 total pulses at 80% active motor threshold) over the motor cortex. Motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) of the first dorsal interosseous muscle were examined before and after TBS. RESULTS: MEPs, SICI, and HFO amplitudes were increased and decreased significantly after iTBS and cTBS, respectively. Wide-band SEPs did not change significantly after TBS. CONCLUSIONS: TBS changed the cortical excitability of the sensorimotor cortices. Changes in HFOs after TBS were parallel to those in SICI. SIGNIFICANCE: The mechanisms of changes in HFOs after TBS may be the same as those in SICI.     

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.     

Congenital hemiparesis: different functional reorganization of somatosensory and motor pathways.

OBJECTIVES: To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. METHODS: We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. RESULTS: TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive-negative-positive, 39-44-48 ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. CONCLUSIONS: Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.     

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.     

Theta burst stimulation does not reliably depress all regions of the human motor cortex

OBJECTIVE: The excitability of the human motor cortex projecting to hand muscles can be reduced by theta burst transcranial magnetic repetitive stimulation (TBS). This study compared the magnitude and variability of changes evoked by TBS for a distal and proximal arm muscle. METHODS: Eight subjects participated in three studies. In each study, electromyographic responses (MEPs) to single-pulse transcranial magnetic stimulation assessed cortical excitability before and after 40s of TBS. In the first two studies, TBS (intensity, 80% active motor threshold) was delivered to the optimal locations for biceps or first dorsal interosseous (FDI). In the final study, weaker intensity TBS was delivered over the biceps representation. RESULTS: TBS targeting biceps produced highly variable results among subjects. For the group, MEPs were not significantly depressed. Repeat studies in individual subjects highlighted the variability of responses. For FDI, MEPs were significantly depressed 5min after TBS and remained depressed for >30min (p<0.05). No significant changes in biceps MEPs occurred with weaker TBS. CONCLUSIONS: The magnitude and reliability of TBS depends on the region of the cortex targeted. SIGNIFICANCE: Results obtained for the hand should not be considered indicative of changes that will occur in other regions of the motor cortex or the brain.     

Dissociation of somatosensory and motor evoked potentials in non-comatose patients after head injury.

OBJECTIVES: This study was performed to evaluate the clinical value of combined use of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in patients with different brain lesions after head trauma. METHODS: A total of 64 patients with minor and moderate head injury were investigated by means of SEPs recorded over the parietal and frontal areas and MEPs following single-pulse transcranial magnetic stimulation (sTMS) and slow-rate repetitive transcranial magnetic stimulation (rTMS). RESULTS: In almost 50% of the patients, a dissociated impairment of somatosensory and motor evoked potentials was found. This dissociation was related to different distribution of SEP and MEP abnormalities in head injury subgroups. The higher threshold to sTMS and increased variability of the MEP amplitude during slow-rate rTMS were the most prominent features in patients with focal brain contusions, suggesting impairment of the cortical excitability. SEP abnormalities, as well as central conduction impairments, were more noticeable in patients with diffuse brain injury. CONCLUSIONS: A combined analysis of SEPs and MEPs may improve the assessment of cortical dysfunctions and central conduction abnormalities in non-comatose patients with head injury. A slow-rate rTMS may be considered as a complementary technique to the evaluation of the threshold in assessment of the excitability of the motor cortex in minor and moderate head injury.     

Parallel inhibition of cortico-muscular synchronization and cortico-spinal excitability by theta burst TMS in humans

OBJECTIVE: To investigate the after-effects of theta burst TMS (TBS) on cortico-muscular synchronization, and on cortico-spinal excitability, in humans. METHODS: We studied 10 healthy subjects using a continuous paradigm of TBS (cTBS), i.e. 600 pulses in 40s. Before and after the cTBS, coherence function was computed as a measure of cortico-muscular synchronization by recording electroencephalogram (EEG) from 19 scalp sites and electromyogram (EMG) from right first dorsal interosseous (FDI) muscle during the isometric contraction. In a separate experiment, motor-evoked potentials (MEPs) in response to single TMS pulses were recorded from the FDI muscle before and after the cTBS, to measure cortico-spinal excitability. RESULTS: When the cTBS was applied over the left primary motor cortex (M1), the beta-band cortico-muscular coherence for the C3 scalp site, as well as the MEP amplitude significantly decreased in 30-60 min, and then recovered to the original levels in 90-120 min. Neither sham stimulation nor cTBS applied over 2 cm posterior to M1 produced significant effects. CONCLUSIONS: cTBS-over-M1 can inhibit the cortico-muscular synchronization in parallel with the decline of cortico-spinal excitability. SIGNIFICANCE: Our results provide the first evidence that TBS can efficiently alter the functional cortico-muscular coupling in humans.     

Transcranial direct current stimulation applied over the somatosensory cortex - differential effect on low and high frequency SEPs.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has an influence on the excitability of the human motor cortex measured by motor evoked potentials (MEPs) after transcranial magnetic stimulation. Low and high frequency (HFOs) components of somatosensory evoked potentials (SEPs) were studied questioning whether a comparable effect can be observed after applying tDCS to the human somatosensory cortex. METHODS: Multichannel median nerve SEPs were recorded before and after applying tDCS of 1mA over a period of 9min with the cathode placed over the somatosensory cortex and the anode over the contralateral forehead and vice versa in a second session. The source activity of the N20, N30 and HFOs was evaluated before and after application of tDCS. RESULTS: After cathodal tDCS to the somatosensory cortex we found a significant reduction of the N20 source amplitude while there was no effect after anodal stimulation. For the N30 component and HFOs no change in source activity was observed. CONCLUSIONS: Corresponding to the results for the motor cortex a sustained reduction of the excitability of the somatosensory cortex after cathodal tDCS was shown. SIGNIFICANCE: We demonstrated differential effects of tDCS on the high and low frequency components of SEPs confirming the hypothesis of locally and functionally distinct generators of these two components.     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society     

Inhibitory transcranial magnetic theta burst stimulation attenuates prefrontal cortex oxygenation

Recent studies highlighted the great potential of newly established theta burst stimulation (TBS) protocols for non‐invasive human brain stimulation studies using transcranial magnetic stimulation (TMS). While intermittent TBS over the primary motor cortex was found to potentiate motor evoked potentials, continuous TBS led to profound attenuations. Although numerous studies investigated the impact of TBS on motor cortex function, yet, only few imaging studies focused on its effects in other brain areas. Particularly for the prefrontal cortex, it is unclear whether TBS has similar effects compared to application over motor areas. In the current study continuous TBS was applied to either the left or right dorsolateral prefrontal cortex in a sample of healthy subjects. Changes in prefrontal oxygenation were measured during an emotional Stroop task by means of functional multi‐channel near‐infrared spectroscopy (fNIRS) before and after stimulation. Results showed bilaterally decreased prefrontal oxygenation following inhibitory stimulation of the left prefrontal cortex but no behavioral effect. No such alterations were observed following right‐hemispheric or sham stimulation. The results of the current study are in line with earlier findings and additionally demonstrate that also prefrontal oxygenation can be impaired by continuous TBS. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

The use of transcranial magnetic stimulation for monitoring descending spinal cord motor function.

This report describes our initial clinical experience using transcranial magnetic stimulation for monitoring spinal cord motor function during surgical procedures. Motor evoked potentials were elicited using a cap shaped coil placed on the scalp of 27 patients while recording peripheral motor responses (compound muscle action potentials--CMAPs) from the upper (N = 1) or lower limbs (N = 26). Wherever possible, cortical somatosensory responses (SEPs) were also monitored by electrically stimulating the left and right posterior tibial nerve (N = 25) or the median nerve (N = 1). The judicious choice of anesthetic regimens resulted in successfully obtaining motor evoked responses (MEPs) in 21 of 27 patients and SEPs in 26 of 27 patients. Single pulse TMS resulted in peripheral muscle responses having large variability, whereas, the variability of SEPs was much less. Criteria based on response variability for assessing clinically significant changes in both MEPs and SEPs resulted in two false negative predictions for SEPs and none for MEPs when evaluating postoperative motor function. We recommend monitoring both sensory and motor pathways during procedures where placing the spinal cord at risk of damage.     

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans

ObjectiveQuadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1).MethodsOne burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5 s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs).ResultsQPS-5 over M1 or dPMC enhanced the P25–N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs.ConclusionsQPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations.SignificanceQPSs induced heterotopic LTP or LTD-like cortical excitability changes.     

Evoked potentials in HIV infection]

The study of the literature data on the multimodal evoked potentials in HIV infected patients shows many abnormalities as well in asymptomatic subjects without AIDS as in AIDS subjects with or without neurological signs. Visual evoked potentials (VEPs) reveal prolonged P100 wave latency in 22% of HIV asymptomatic subjects and in 26% of HIV symptomatic subjects; brainstem auditory evoked potentials (BAEPs) reveal an increase of the interpeak latency I-V in 16% of asymptomatic subjects and in 32% of symptomatic subjects; somatosensory evoked potentials (SEPs) by median nerve stimulation reveal prolonged central conduction time in 6% of asymptomatic subjects and in 11% of symptomatic subjects; somatosensory evoked potentials (SEPs) by tibial nerve stimulation reveal prolonged central conduction time in 4% of asymptomatic subjects and in 45% of symptomatic subjects; motor evoked potentials (MEPs) by magnetic stimulation reveal prolonged central motor conduction time in 46% of asymptomatic subjects.     

Somatosensory evoked potentials and high frequency oscillations are differently modulated by theta burst stimulation over primary somatosensory cortex in humans

Objective

The effects of theta burst stimulation (TBS) have been extensively investigated in primary motor cortex, where it leads to long-lasting LTP/LTD-like effects on synaptic plasticity. This study aimed to extend these observations to sensory cortex.

Methods

Fourteen healthy subjects participated in the study. Conditioning 600-pulse intermittent TBS (iTBS) and continuous TBS (cTBS) were delivered to left somatosensory cortex (S1) with an intensity of 80% active motor threshold. Somatosensory evoked potentials (SEPs) were evoked by median nerve electrical stimulation at right wrist. High frequency oscillations (HFOs) were obtained by digital filtering of original SEPs and divided into early and late subcomponents, relative to N20_peak latency.

Results

Repeated-measures ANOVA showed that iTBS facilitated N20_onset–N20_peak at 15 min and N20_peak–P25 at 15 and 30 min after conditioning, whereas cTBS did not. iTBS left the early and late HFOs unchanged. Conversely, cTBS facilitated the early HFOs, whereas it inhibited the late HFOs at 15 min after conditioning.

Conclusions

S1-iTBS facilitated SEPs without changes in HFOs whereas cTBS modulated early and late HFOs without changes in SEPs.

Significance

S1-TBS produces lasting changes in the excitability of intracortical circuits generating SEPs and HFOs differentially through mechanisms of LTP/LTD-like synaptic plasticity.     

Sensorimotor central conduction time in comatose patients.

Motor evoked potentials (MEPs) following magnetic stimulation were recorded in 22 patients comatose as a result of head injury (13 cases), stroke (7 cases) or anoxia (2 cases). Somatosensory evoked potentials (SEPs) from median nerve were recorded as well in 19 cases in the same session. Thirteen patients died or remained vegetative (59.1%), 3 were severely disabled (13.6%) and 6 showed a good recovery (27.3%). MEPs were significantly related to the outcome; they appeared to be a more accurate prognostic indicator than the Glasgow Coma Scale (GCS). However, 1 out of 6 patients with bilaterally absent MEPs (16.7%) showed a good recovery. SEPs were significantly related to the outcome as well, but the combined use of SEP and MEP improved the outcome prediction, decreasing the rate of false negatives. Two patients had normal sensorimotor function, 13 a combined sensorimotor dysfunction, while 4 had a pure motor dysfunction. Our results suggest that SEPs and MEPs may improve the assessment of sensorimotor dysfunction in comatose patients. A significant relationship between MEPs and outcome appears to exist, but the assessment of MEP reliability requires further study.     

Inhibition of motor system excitability at cortical and spinal level by tonic muscle pain.

OBJECTIVE: To assess whether the motor system excitability can be modified by experimental tonic pain induced either in muscles or in subcutis. METHODS: Transcranial magnetic stimulation of the left primary motor cortex was used to record motor evoked potentials (MEPs) from the right abductor digiti minimi (ADM) muscle. Recordings were made before, during and after experimental pain induced by (1) injection of hypertonic (5%) saline into the right ADM, the right first dorsal interosseum (FDI) and the left ADM muscles, and (2) injection of hypertonic saline in the subcutaneous region of the right ADM. Both MEPs and H-reflex were recorded also from the right flexor carpi radialis (FCR) before, during and after muscle pain. RESULTS: MEPs recorded from the ADM muscle were significantly reduced in amplitude during pain induced in the right ADM and right FDI muscles, but not during pain in the left ADM muscle or during subcutaneous pain. This inhibitory effect was observed during the peak-pain and persisted also after the disappearance of the pain sensation. In the FCR muscle, the MEP inhibition was observed during the peak-pain, while a significant reduction of the H-reflex's amplitude was observed starting 1 min after the peak-pain. CONCLUSIONS: Tonic muscle pain can inhibit the motor system. The motor cortex inhibition observed at an early phase is followed by a reduction of the excitability of both cortical and spinal motoneurones.     

Effects of musical training on speech-induced modulation in corticospinal excitability

We investigated the effect of previous musical training on lateralization of language as indexed by the effects of reading aloud on the modulation of motor evoked potentials (MEPs) induced in the first dorsal interosseus muscles (FDI) by transcranial magnetic stimulation (TMS) of the primary motor cortex. We studied 13 right-handed subjects, seven musicians who had been playing a musical instrument for >10 years and six controls who had never studied a musical instrument. In all subjects, the amplitude of MEPs in the right FDI was facilitated by reading aloud. However, the musicians also showed significant facilitation in the left FDI, while controls did not. These results illustrate striking effects of musical training on lateralization of motor and language functions.     

Delayed facilitation of motor cortical excitability following repetitive finger movements.

OBJECTIVES: To define motor cortical excitability changes occurring at various times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty healthy right-handed subjects were studied with transcranial magnetic stimulation (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s) repetitive opening-closing bilateral movements of the index finger onto the thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI) and rate of the repetitive finger movements were determined (1) before exercise, (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a subsequent 30 min rest period. RESULTS: Rate of movement did not show significant change during any of the exercise periods but did increase significantly when tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were facilitated whereas MEPs after 90 s of exercise did not differ from baseline measures. MEP amplitudes were significantly increased after rest of approximately 15 min compared to the baseline MEPs. In contrast, motor potentials evoked by peripheral nerve stimulation were unchanged throughout the experimental test periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger muscle (FDI) was facilitated beginning 15 min after a brief period of non-forceful, repetitive activity of that muscle. This delayed facilitation of motor cortex after exercise may represent a form of short-term potentiation of motor cortical excitability.     

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.     

Motor and somatosensory evoked potentials in asymptomatic spondylotic cord compression.

To assess whether electrophysiological tests are of use in differentiating between patients with asymptomatic cervical stenosis and patients with clinical evidence of myelopathy, we studied motor evoked potentials (MEPs) to magnetic brain stimulation and somatosensory evoked potentials (SEPs) in patients with asymptomatic cervical cord compression and compared the results to healthy age-matched controls. The MEPs were normal in 23 of 25 patients and SEPs in 22 of 23 patients. Thus, MEPs and SEPs are normal in most cases of asymptomatic cervical stenosis. As previous studies have shown MEPs, and to a lesser extent SEPs, to be sensitive in the detection of spondylotic myelopathy, our data indicate that MEP and SEP may be clinically useful for differentiating patients with cervical stenosis who have myelopathy from those who have not.