Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials.

OBJECTIVE: To study the after-effect of theta burst stimulation (TBS) over the left sensorimotor cortex on the size of somatosensory as well as motor evoked potentials evoked from both hemispheres in healthy human subjects. METHODS: We used a continuous TBS paradigm for 40 s (600 pulses) in which a burst of 3 transcranial magnetic stimuli at 50 Hz is repeated at 5 Hz [Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron 2005;45:201-6]. Somatosensory evoked potentials (SEPs) following electrical stimulation of right or left median nerve and motor evoked potentials (MEPs) in the right or left first dorsal interosseous (FDI) muscles were recorded before and after TBS over the left motor cortex (M1) or a point 2 cm posterior to left M1. RESULTS: Amplitudes of P25/N33 (parietal components) following right median nerve stimulation were significantly increased for at least 53 min after TBS over the left M1, whereas this component was suppressed for 13 min after TBS over a point 2 cm posterior. MEPs in right as well as left FDI muscles were suppressed with a similar time course after TBS over the left M1. CONCLUSIONS: A single-session of TBS over the sensorimotor cortex can induce a short-lasting change in the size of ipsilateral cortical components of SEPs as well as MEPs evoked from both hemispheres. SIGNIFICANCE: TBS is an interventional tool that can induce rapid reorganization within cortical somatosensory as well as motor networks 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.     

Cervical spine manipulation alters sensorimotor integration: a somatosensory evoked potential study.

OBJECTIVE: To study the immediate sensorimotor neurophysiological effects of cervical spine manipulation using somatosensory evoked potentials (SEPs). METHODS: Twelve subjects with a history of reoccurring neck stiffness and/or neck pain, but no acute symptoms at the time of the study were invited to participate in the study. An additional twelve subjects participated in a passive head movement control experiment. Spinal (N11, N13) brainstem (P14) and cortical (N20, N30) SEPs to median nerve stimulation were recorded before and for 30min after a single session of cervical spine manipulation, or passive head movement. RESULTS: There was a significant decrease in the amplitude of parietal N20 and frontal N30 SEP components following the single session of cervical spine manipulation compared to pre-manipulation baseline values. These changes lasted on average 20min following the manipulation intervention. No changes were observed in the passive head movement control condition. CONCLUSIONS: Spinal manipulation of dysfunctional cervical joints can lead to transient cortical plastic changes, as demonstrated by attenuation of cortical somatosensory evoked responses. SIGNIFICANCE: This study suggests that cervical spine manipulation may alter cortical somatosensory processing and sensorimotor integration. These findings may help to elucidate the mechanisms responsible for the effective relief of pain and restoration of functional ability documented following spinal manipulation treatment.     

Influence of stimulus repetition rate on cortical somatosensory potentials evoked by median nerve stimulation: implications for generation mechanisms.

Despite growing clinical and experimental interest in the cortical components of somatosensory evoked potentials (SEPs) little is known about their physiological dynamics, e.g. with changing stimulation parameters. This paper reports the influence of varying stimulus repetition rate from 0.5 to 5 Hz on cortical SEPs up to 60-msec latency after right median nerve stimulation, separately analyzed at frontal (F3), central (C3) and parietal (P3) electrodes. The amplitudes of early frontal P20 and N25, central P14 and N18, and parietal N20 did not change with stimulation rate. Later deflections were significantly modified when their amplitudes were determined with respect to the baseline: at F3 negative N30 and N60 diminished and positive P40 was enhanced with increasing rate of stimulation. At P3 the effects were the reverse, so that positive P27 and P45 were attenuated while negative N34 and N60 were enhanced. At C3 both positive P22 and P40 and negative N60 were reduced. However, the corresponding peak-to-peak amplitudes changed much less. We conclude that SEP waveforms following the earliest cortical deflections are very sensitive to small changes in stimulation frequency. The opposite changes at F3 compared with P3 probably represent the opposite scalp field poles from horizontally oriented generator(s) located within the primary sensorimotor cortex (SMI). We suggest that the rate effects are partly due to selective sensitivity of postexcitatory inhibitory postsynaptic potentials to stimulation frequency.     

Focal capsular vascular lesions can selectively deafferent the prerolandic or the parietal cortex: somatosensory evoked potentials evidence

Four patients with a unilateral focal vascular accident involving the internal capsule (but not the cortex) were studied electrophysiologically. Averaged somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve on the left or the right side were analyzed. In the 3 patients with hemiparesis and normal somatic sensation, the precentral P22 and N30 SEP components were lost, whereas the parietal components were preserved. In another patient with clinical somatosensory loss unaccompanied by any central motor impairment, the precentral SEP components were preserved, whereas the parietal SEP components were lost. Thus, a small capsular lesion can eliminate distinct cortical SEP components by selectively involving either the axons of the thalamic VPLc nucleus going to parietal receiving cortex or the axons of thalamic VPLo going to motor area 4. These findings extend to subcortical lesions the diagnostic value of SEPs in patients with dissociated clinical motor and sensory signs.     

Scalp-recorded short and middle latency peroneal somatosensory evoked potentials in normals: comparison with peroneal and median nerve SEPs in patients with unilateral hemispheric lesions

Peroneal somatosensory evoked potentials (SEPs) were performed on 23 normal subjects and 9 selected patients with unilateral hemispheric lesions involving somatosensory pathways. Recording obtained from right and left peroneal nerve (PN) stimulations were compared in all subjects, using open and restricted frequency bandpass filters. Restricted filter (100-3000 Hz) and linked ear reference (A1-A2) enhanced the detection of short latency potentials (P1, P2, N1 with mean peak latency of 17.72, 21.07, 24.09) recorded from scalp electrodes over primary sensory cortex regions. Patients with lesions in the parietal cortex and adjacent subcortical areas demonstrated low amplitude and poorly formed short latency peroneal potentials, and absence of components beyond P3 peak with mean latency of 28.06 msec. In these patients, recordings to right and left median nerve (MN) stimulation showed absence or distorted components subsequent to N1 (N18) potential. These observations suggest that components subsequent to P3 potential in response to PN stimulation, and subsequent to N18 potential in response to MN stimulation, are generated in the parietal cortical regions.     

Differences of cortical activation in spontaneous and reflex myoclonias.

Frontal and parietal components of somatosensory evoked potentials (SEPs) following median nerve stimulation and scalp potentials preceding myoclonic jerks (jerk-locked averaging, JLA) were compared in 6 patients with cortical reflex myoclonus. Giant potentials were found over the parietal cortex in both conditions. Prominent frontal activity was detected following median nerve stimulation which, however, was absent in jerk-locked averages. Therefore an identical generator of the giant SEP and the JLA is unlikely. As the frontal component is lacking in jerk-locked averaging, the spontaneous jerks produced in our experimental paradigm are believed to be due to spontaneous hyperactivity of the parietal cortex rather than to pathologically enhanced transcortical reflexes.     

Somatosensory evoked high-frequency oscillations recorded directly from the human cerebral cortex.

OBJECTIVE: To elucidate the generator sources of high-frequency oscillations of somatosensory evoked potentials (SEPs), we recorded somatosensory evoked high-frequency oscillations directly from the human cerebral cortex. SUBJECTS AND METHODS: Seven patients, 6 with intractable partial epilepsy and one with a brain tumor, were studied. With chronically implanted subdural electrodes, we recorded SEPs to median nerve stimulation in all patients, and also recorded SEPs to lip and posterior tibial nerve stimulation in one. High-frequency oscillations were recorded using a restricted bandpass filter (500-2000 Hz). RESULTS: For the median nerve oscillations, all oscillation potentials were maximum at the electrodes closest to the primary hand sensorimotor area. Most oscillations were distributed similar to or more diffusely than P20/N20. Some later oscillations after the peak of P20 or N20 were present in a very restricted cortical area similar to P25. We investigated the phase change of each oscillation potential around the central sulcus. One-third of the oscillations showed phase reversal around the central sulcus, while later oscillations elicited in a restricted cortical area did not. High-frequency oscillations to posterior tibial nerve and lip stimulation were also maximum in the sensorimotor areas. Most of the lip oscillations showed phase reversal around the central sulcus, but most of the posterior tibial nerve oscillations did not. CONCLUSION: High-frequency oscillations are generated near the primary sensorimotor area. There are at least two different generator mechanisms for the median nerve high-frequency oscillations. We suspect that most oscillations are derived from the terminal segments of thalamocortical radiations or from the primary sensorimotor cortex close to the generator of P20/N20, and some later oscillations from the superficial cortex close to the generator of P25.     

Vibratory stimulation of proximal muscles does not affect cortical components of somatosensory evoked potential following distal nerve stimulation.

OBJECTIVES: The effects of the proprioceptive activity of the proximal muscles on somatosensory evoked potentials (SEPs) were investigated, using vibratory stimulation of proximal muscle tendons. METHODS: SEPs were recorded following electrical median nerve stimulation at the wrist during vibratory stimulation of tendon of pronator teres, biceps and trapezius muscles and fingers in 8 normal subjects. RESULTS: The cortical SEP components, N20, P25 and N33 recorded from the parietal area, and P20 and N30 recorded from frontal area contralateral to the stimulated side, were markedly attenuated by vibratory stimulation applied to the fingers, but unaffected by vibratory stimulation of the proximal muscles. CONCLUSION: The proprioceptive afferent, especially group Ia muscle spindle afferent, in the relaxed proximal muscles is not likely to contribute to the gating of SEP following distal nerve stimulation.     

Right or left ear reference changes the voltage of frontal and parietal somatosensory evoked potentials.

Short-latency cortical somatosensory evoked potentials (SEPs) to left median nerve stimulation were recorded with either the left or right earlobe as reference. With a right earlobe reference the voltage of the parietal N20 and P27 was reduced while the voltage of the frontal P20 and N30 was enhanced. The effects were consistent, but their size varied with the SEP component considered and also among the subjects. Analysis of SEPs at different scalp sites and at either earlobe suggested that the ear contralateral to the side stimulated picked up transient potential differences, depending a.o. on side asymmetry and geometry of the neural generators as disclosed in topographic mapping. For example, the right ear potential can be shifted negatively by the right N20 field evoked by left median nerve stimulation. The changes involve the absolute potential values, but not the time features or the gradients of potential fields. Scalp current density (SCD) maps are not affected. The results are pertinent for current discussions about which reference to use and document the practical recommendation of recording short-latency cortical SEPs with a reference at the ear ipsilateral (not contralateral) to the side of stimulation.     

Frontal and parietal components of enhanced somatosensory evoked potentials: a comparison between pathological and pharmacologically induced conditions

Pathologically enhanced somatosensory evoked potentials (giant SEPs) were recorded in 10 patients with cortical myoclonus of various origins. With non-cephalic reference electrodes a giant frontal negativity corresponding to normal N30 was found over the contra- and ipsilateral hemispheres which was not simply a phase reversal of the well-known enhanced parietal P25. The preceding far-field P14, parietal N20 and frontal P22 were of normal size. A similar result was found when SEPs were studied during the action of etomidate, an ultrashort-acting non-barbiturate hypnotic which produced a marked increase of the parietal P25 and frontal N30 after intravenous administration. These increased components, on the other hand, were abolished when recording was repeated immediately after application of electroconvulsive shock whereas P14, N20, and P22 remained more or less unchanged in both conditions. Our results indicate that there are neuronal elements in the sensorimotor cortex which are more resistant to influences such as narcotic drugs and seizure activity than others, being highly modifiable by these alterations. It is speculated whether these highly modifiable cortical systems are those in which giant SEPs, as well as pharmacologically increased SEP components, arise.     

The relationship between human long-latency somatosensory evoked potentials recorded from the cortical surface and from the scalp.

In scalp recordings, stimulation of the median nerve evokes a number of long-latency (40-300 msec) somatosensory evoked potentials (SEPs) whose neural origins are unknown. We attempted to infer the generators of these potentials by comparing them with SEPs recorded from the cortical surface or from within the brain. SEPs recorded from contralateral sensorimotor cortex can be characterized as "precentral," "postcentral," or "pericentral." The scalp-recorded P45, N60 and P100 potentials appear to correspond to the pericentral P50, N90 and P190 potentials and are probably generated mainly in contralateral area 1 of somatosensory cortex. The scalp-recorded N70-P70 appear to correspond to the precentral and postcentral N80-P80 and are generated mainly in contralateral area 3b of somatosensory cortex. The scalp-recorded N120-P120 appear to correspond to the intracranial N100-P100 and are probably generated bilaterally in the second somatosensory areas. N140 and P190 (the "vertex potentials") are probably generated bilaterally in the frontal lobes, including orbito-frontal, lateral and mesial (supplementary motor area) cortex. The supplementary sensory area probably generates long-latency SEPs, but preliminary recordings have yet to confirm this assumption. Most of the proposed correspondences are speculative because the different conditions under which scalp and intracranial recordings are obtained make comparison difficult. Human recordings using chronically implanted cortical surface electrodes, and monkey studies of SEPs which appear to be analogs of the human potentials, should provide better answers regarding the precise generators of human long-latency SEPs.     

Origin of frontal N15 component of somatosensory evoked potential in man

Origin of the frontal somatosensory evoked potential (SEP) by median nerve stimulation was investigated in normal volunteers and in patients with localized cerebrovascular diseases, and the following results were obtained. (1) In normal subjects, SEPs recorded at F3 (or F4) contralateral to the stimulating median nerve were composed of P12, N15, P18.5 and N26. Similar components were recognized in SEP recorded at Fz. (2) In patients in whom putaminal or thalamic hemorrhages had destroyed the posterior limbs of the internal capsules, frontal N15 and parietal N18 (N20) disappeared. These components were also absent in patients with cortical (parietal) infarctions. Among these patients, the thalamus was not affected in cases with putaminal hemorrhages and cortical infarctions. These facts indicate that the generator of the frontal N15 does not exist in the thalamus but that it originates from the neural structure central to the internal capsule, which suggests a similarity to the generator of the parietal N18. Because N15 was recorded in the midline of the frontal region with shorter latency than parietal N18, the frontal N15 might represent a response to the sensory input of the frontal lobe via the non-specific sensory system.     

Cortical and subcortical somatosensory evoked potentials to median nerve stimulation in man

In order to define the precise locations of precentral and postcentral gyri during neurosurgical operations, somatosensory evoked potentials to contralateral median nerve stimulation were recorded from the cerebral cortex in 19 cases with organic cerebral lesions which located near the central sulcus. In addition to that, distribution patterns of early components of SEPs were displayed by Nihonkoden Atac 450 in 3 cases who had bone defects after wide decompressive craniectomy but were without any sensory disturbances In 4 cases, in whom deep electrodes were inserted for the stereotaxic operations or other reasons, frontal subcortical SEPs were recorded in order to know the origins of frontal components of SEPs. From the parietal cortex, N19, P22 and P23 were observed. And from the frontal cortex, P20 and N25 were obtained. Their average peak latencies were as follows; (table; see text) Because all subjects had organic lesion in the brain, the peak latencies were a little bit longer, and their standard deviations were larger than those in normal cases. Usually, clear-cut phase reversal could be observed between N19 and P20 across the central sulcus. So, the precentral and postcentral gyri were easily identified during the operations. N19 and P23 appeared over the wide areas of the parietal cortex. Also, P20 and N25 were recorded almost whole areas of the frontal cortex. On the other hand, P22 appeared from relatively restricted part of the postcentral gyrus where sensory hand area might have been located. Depth recording from the frontal subcortical area revealed that P20 could be recorded from the bilateral frontal subcortical areas and there observed no phase reversal between the cortical and subcortical SEPs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine.

OBJECTIVES: To determine whether conventional as well as high-frequency somatosensory evoked potentials (SEPs) to upper limb stimulation are influenced by GABAergic intracortical circuitry. METHODS: We recorded SEPs from 6 healthy volunteers before and after a single-oral administration of tiagabine. Conventional low-frequency SEPs have been obtained after stimulation of the median nerve, as well as after stimulation of the first phalanx of the thumb, which selectively involves cutaneous finger inputs. Median nerve SEPs have been further analyzed after digital narrow-bandpass filtering, to selectively examine high-frequency responses. Lastly, in order to explain scalp SEP distribution before and after tiagabine administration, we performed the brain electrical source analysis (BESA) of raw data. RESULTS: After tiagabine administration, conventional scalp SEPs showed a significant amplitude increase of parietal P24, frontal N24 and central P22 components. Similarly, BESA showed a significant strength increase of the second peak of activation of the first two perirolandic dipoles, which are likely to correspond to the N24/P24 and P22 generators. By contrast, no significant changes of high-frequency SEPs were induced by drug intake. CONCLUSIONS: Our findings support the view that both N24/P24 and P22 SEP components are probably generated by deep spiny cell hyperpolarization, which is strongly increased by inhibitory inputs from GABAergic interneurons. By considering the clear influence of inhibitory circuitry in shaping these SEP components, conventional scalp SEP recording could be useful in the functional assessment of the somatosensory cortex in different physiological and pathological conditions. By contrast, intrinsic firing properties of the cell population generating high-frequency SEP responses are unaffected by the increase of recurrent GABAergic inhibition.     

Magnetoencephalographic investigation of somatosensory homunculus in patients with peri-Rolandic tumors

In order to investigate functional topography of the hand somatosensory cortex in five patients with peri-Rolandic tumors (four frontal lobes and one parietal lobe), we recorded somatosensory evoked fields (SEFs) using magnetoencephalography (MEG) after stimulation of the median nerve (MN) and the five digits. The results obtained were compared with those of five normal healthy subjects. In all five patients, SEFs following MN and digit stimulation showed the previously described respective N20m and N22m components of primary sensory response. Single dipole modeling was applied to determine the three dimensional cortical representations of the N20m and N22m components. The cortical representations of the hand were identical to those of normal subjects, arranging in an orderly somatotopic way from lateral inferior to medial superior in the sequence thumb, MN, index, middle, ring, and little fingers. This sensory homunculus was confirmed by cortical recording of the somatosensory evoked potentials (SEPs) at the time of surgery. Thus, we demonstrate that SEFs, recorded on MEG in conjunction with source localization techniques, are useful to non-invasively investigate the functional topography of the human hand somatosensory cortex in pathological conditions.     

Abnormal gating of somatosensory inputs in essential tremor.

OBJECTIVE: To study whether sensorimotor cortical areas are involved in Essential Tremor (ET) generation.BACKGROUND: It has been suggested that sensorimotor cortical areas can play a role in ET generation. Therefore, we studied median nerve somatosensory evoked potentials (SEPs) in 10 patients with definite ET.METHODS: To distinguish SEP changes due to hand movements from those specifically related to central mechanisms of tremor, SEPs were recorded at rest, during postural tremor and during active and passive movement of the hand. Moreover, we recorded SEPs from 5 volunteers who mimicked hand tremor. The traces were further submitted to dipolar source analysis.RESULTS: Mimicked tremor in controls as well as active and passive hand movements in ET patients caused a marked attenuation of all scalp SEP components. These SEP changes can be explained by the interference between movement and somatosensory input ('gating' phenomenon). By contrast, SEPs during postural tremor in ET patients showed a reduction of N20, P22, N24 and P24 cortical SEP components, whereas the fronto-central N30 wave remained unaffected.CONCLUSIONS: Our findings suggest that in ET patients the physiological interference between movement and somatosensory input to the cortex is not effective on the N30 response. This finding thus indicates that a dysfunction of the cortical generator of the N30 response may play a role in the pathogenesis of ET.     

Middle-latency somatosensory evoked potentials after stimulation of the radial and median nerves: component structure and scalp topography.

Somatosensory evoked potentials (SEPs) after radial nerve stimulation are studied less frequently than those after median nerve stimulation. Therefore, little is known about their component structure and scalp topography. We investigated radial nerve SEPs after electrical stimulation at the left wrist. For comparison, the median nerve was also stimulated at the wrist. SEPs were recorded with 15 scalp electrodes (bandpass 0.5-200 Hz) in 27 healthy subjects. The waveform of the radial nerve SEP at a contralateral parietal lead was comparable to that of the median nerve SEP, consisting of P14, N20, P30, and N60. In spite of comparable stimulus intensities, SEP amplitudes were smaller after radial than after median nerve stimulation. Significant latency differences were found only for N20 (earlier for median nerve) and P30 (earlier for radial nerve). The duration of the primary complex N20-P30 thus was significantly shorter for the radial nerve. Whereas N20 and P30 were present with either earlobe or frontal reference, N60 had a prerolandic maximum and was best recorded with a bipolar transverse derivation. In addition, another middle-latency negativity (N110) was found near the secondary somatosensory cortex, which had previously been described only for radial nerve stimulation. In standard SEP derivations, the N110 is riding on the ascending limb of the vertex negativity. It could best be recorded in low temporal leads versus a midline reference. The scalp topographies of P30, N60, and N110 were similar for radial and median nerve stimulation.     

Intra-operative optical method using intrinsic signals for localization of sensorimotor area in patients with brain tumor.

The purpose of this study is intra-operatively to localize the sensorimotor area by intrinsic optical method detecting the changes in regional cerebral blood flow (rCBF) and cortical temperature following neuronal activity during median nerve stimulation. In 18 patients with brain tumors located around the sensorimotor cortex, cortical recording of somatosensory evoked potentials (SEPs) was performed and localized changes in rCBF during median nerve stimulation were measured by a laser-Doppler flowmeter on the locations of SEPs and around the activation area obtained by functional magnetic resonance imaging (fMRI). In two patients, cortical thermomapping was also performed during median nerve stimulation. In fMRI study, the significant activation area of sensorimotor could be obtained in 17 of 18 patients. In cortical recording of SEPs, the polarity reversal of N20 and P20 was observed in 14 of the 18 patients. In 9 of the 14 patients in whom SEPs could be recorded, the localized changes in rCBF, corresponding to the stimulation, were detected in the N20 area. In 2 of the 4 patients in whom N20 could not be recorded successfully, the localized changes in rCBF could be detected. The increase in rCBF during the stimulation was 18.3% +/- 5.3% (mean +/- SD, n = 11). Thermomapping could demonstrate the localized area, where the increase in rCBF was also detected, by observation of the changes in cortical temperature during the stimulation. The intra-operative intrinsic optical method detecting rCBF and cortical temperature in combination with recording of SEPs may be considered useful for brain functional localization related to neurosurgical disorders.     

Modification of cortical somatosensory evoked potentials during tactile exploration and simple active and passive movements.

The present study compares the effects of different types of movement on median nerve somatosensory evoked potentials (SEPs) recorded from frontal, central and parietal electrodes. Test conditions included tactile exploratory movements, repetitive active and passive thumb movements and isometric contraction. All these conditions modified the SEPs in a similar manner. Parietal N20, P25, and N60, central P22 and N32, and frontal N25, N30 and P40 deflections were diminished, while later centro-parietal P40 and fronto-central N60 were unchanged. A small frontal P35 emerged during movement. The subcortical P14 was not changed in any of the conditions. The similar modulatory effects of simple active movements and of tactile exploration indicate that the modification of SEPs does not depend on the importance of proprioceptive feedback information for movement execution. As all modulatory effects were present also during passive movement, these observed effects are most likely to be caused by afferent occlusion in the ascending thalamo-cortical pathways or sensorimotor cortical cell populations.