Somatosensory evoked potentials recorded from the human pedunculopontine nucleus region

The pedunculopontine nucleus region (PPNR) is an integral component of the midbrain locomotor region and has widespread connections with the cortex, thalamus, brain stem, cerebellum, spinal cord, and especially, the basal ganglia. No previous study examined the somatosensory connection of the PPNR in human. We recorded somatosensory evoked potentials (SEP) from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in the PPNR in 8 patients (6 with Parkinson's disease, 2 with progressive supranuclear palsy). Monopolar recordings from the PPNR contacts showed triphasic or biphasic potentials. The latency of the largest negative peak was between 16.8 and 18.7 milliseconds. Bipolar derivation revealed phase reversal with median nerve stimulation contralateral to the DBS electrode in 6 patients. There was no difference in SEP amplitude and latency between on and off medication states. We also studied the high frequency oscillations (HFOs) by filtering the signal between 500 and 2,500 Hz. The HFOs could be identified only from contralateral stimulation and had intraburst frequencies of 1061 ± 121 Hz, onset latencies of 13.8 ± 1.2 milliseconds, and burst durations of 7.3 ± 1.1 milliseconds. Among the 10 recordings with HFOs, only 1 had possible phase reversal in the bipolar derivation. Our results suggest that there are direct somatosensory inputs to the PPNR. The slow components and HFOs of the SEP have different origins. © 2010 Movement Disorder Society.     

Cortical potentials evoked by epidural stimulation of the cervical and thoracic spinal cord in man

Scalp somatosensory evoked potentials (SEPs) were recorded after electrical stimulation of the spinal cord in humans. Stimulating electrodes were placed at different vertebral levels of the epidural space over the midline of the posterior aspect of the spinal cord. The wave form of the response differed according to the level of the stimulating epidural electrodes. Cervical stimulation elicited an SEP very similar to that produced by stimulation of upper extremity nerves, e.g., bilateral median nerve SEP, but with a shorter latency. Epidural stimulation of the lower thoracic cord elicited an SEP similar to that produced by stimulation of lower extremity nerves. The results of upper thoracic stimulation appeared as a mixed upper and lower extremity type of SEP. The overall amplitudes of SEPs elicited by the epidural stimulation were higher than SEPs elicited by peripheral nerve stimulation. In 4 patients the CV along the spinal cord was calculated from the difference in latencies of the cortical responses to stimulation at two different vertebral levels. The CVs were in the range of 45-65 m/sec. The method was shown to be promising for future study of spinal cord dysfunctions.     

High-frequency oscillations in somatosensory system.

The recent revival of interest in high-frequency oscillation (HFO) is triggered by getting an opportunity to noninvasively monitor the timing of highly synchronized and rapidly repeating population spikes generated in the human somatosensory system. HFOs could be recorded from brainstem, cuneothalamic relay neurons, thalamus, thalamocortical radiation, thalamocortical terminals and cortex with deep brain or surface electrodes, or with magnetoencephalography. Here we briefly review the HFOs at each level of somatosensory pathways. HFOs recorded at brainstem might be produced by volume conduction from oscillations of the medial lemniscus. Thalamic HFOs at around 1000 Hz frequency would be generated within the somatosensory thalamus. Cortical HFOs would be generated by at least a few different mechanisms, thalamo-cortical projection terminals, interneurons and pyramidal cells of the primary sensory cortex. HFOs have been studied in several ways: their modulation by arousal changes, movements or drugs, their recovery function, effects of transcranial magnetic stimulation on them and also their changes in patients with various neurological diseases.     

Unmasking of presynaptic and postsynaptic high-frequency oscillations in epidural cervical somatosensory evoked potentials during voluntary movement.

OBJECTIVE: To investigate the effect of the voluntary movement on the amplitude of the somatosensory evoked potentials (SEPs) recorded by an epidural electrode at level of the cervical spinal cord (CSC). METHODS: Fourteen patients underwent an epidural electrode implant at CSC level for pain relief. After the median nerve stimulation, SEPs were recorded from the epidural electrode and from 4 surface electrodes (in frontal and parietal regions contralateral to the stimulated side, over the 6th cervical vertebra, and on the Erb's point). SEPs were recorded at rest and during a voluntary flexo-extension movement of the stimulated wrist. Beyond the low-frequency SEPs, also the high-frequency oscillations (HFOs) were analysed. RESULTS: The epidural electrode contacts recorded a triphasic potential (P1-N1-P2), whose negative peak showed the same latency as the cervical N13 response. The epidural potential amplitude was significantly decreased during the voluntary movement, as compared to the rest. Two main HFOs were identifiable: (1) the 1200 Hz HFO which was significantly lower in amplitude during movement than at rest, and (2) the 500 Hz HFO which was not modified by the voluntary movement. CONCLUSIONS: The low-frequency cervical SEP component is subtended by HFOs probably generated by: (1) postsynaptic potentials in the dorsal horn neurones (1200 Hz), and (2) presynaptic ascending somatosensory inputs (500 Hz). SIGNIFICANCE: Our findings show that the voluntary movement may affect the somatosensory input processing also at CSC level.     

Comparison of somatosensory evoked high-frequency oscillations after posterior tibial and median nerve stimulation.

OBJECTIVE: We compared the high-frequency oscillations (HFOs) evoked by posterior tibial nerve (PTN) and median nerve (MN) stimulation. METHODS: Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000 Hz to right PTN and to right MN stimulation in 10 healthy subjects. The HFOs were obtained by digitally filtering the wide-band SEPs with a band-pass of 300-900 Hz. RESULTS: HFOs were recorded in 8 of the 10 subjects for PTN, and in all subjects for MN stimulation. The HFOs after both PTN and MN stimulation started approximately at or after the onset of the primary cortical response (P37 and N20) and ended around the middle of the second slope. HFO amplitudes and area after PTN stimulation were significantly smaller than those after MN stimulation. HFO duration after PTN stimulation was markedly longer than that after MN stimulation. However, HFO interpeak latencies did not differ between the two nerves. CONCLUSIONS: The present findings suggest that the HFOs after PTN and MN stimulation reflect a neural mechanism common to the hand and foot somatosensory cortex.     

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

OBJECTIVE: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN). METHODS: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS. RESULTS: A large SEP with a mean latency of 17.9+/-1.7 ms was recorded from thalamic contacts. Phase reversal occurred at the horizontal level of the anterior commissure-posterior commissure line. Smaller potentials with similar latency but no reversal could be recorded from STN electrodes. CONCLUSIONS: We propose that the thalamic SEP is generated by excitatory post-synaptic potentials in sensory relay neurons in nucleus ventrocaudalis. A small potential in STN at a similar latency, may be due to volume conduction from thalamus. Intraoperative and postoperative SEP recordings from DBS electrodes could be used to determine the optimal position of the contacts relative to the sensory pathways and the choice of contacts for chronic stimulation.     

Somatosensory evoked potentials after stimulation of digital nerves in upper limbs: normative data

Normative data for somatosensory evoked potentials (SEPs) after stimulation of digital nerves from the first, third and fifth digits, which reach the spinal cord through C6, C7 and C8 roots are presented in 20 normal adults. SEP peak latencies and amplitudes are indicated for Erb's point, the level of the seventh and second cervical vertebrae and contralateral cortical hand area.     

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.     

Spine and scalp somatosensory evoked potentials in normal subjects and patients with spinal cord disease: evaluation of afferent transmission

Spine and scalp somatosensory evoked potentials (SEPs) to peroneal nerve stimulation were recorded from 20 normal subjects using 1 restricted and 3 open frequency filter bandpasses. Spine to spine and spine to scalp propagation velocities were calculated. Of those recording parameters investigated, optimal recordings were obtained using an open bandpass (5-1500 or 30-1500 Hz) and recording from 3 surface spine bipolar channels and 1 scalp bipolar channel. This method was then investigated in 40 patients with disease of the spinal cord and peripheral nervous system. Focal spinal cord compressive lesions generally resulted in slowing of spine to spine and spine to scalp propagation velocities. Diffuse or multifocal lesions of the spinal cord generally resulted in the absence of scalp responses. Although there was no consistent correlation of the SEP findings with the sensory exam, there was a correlation of the SEP findings with the clinical prognosis.     

Parietal generators of low- and high-frequency MN (median nerve) SEPs: data from intracortical human recordings.

OBJECTIVE: To identify low and high-frequency median nerve (MN) somatosensory evoked potential (SEP) generators by means of chronically implanted electrodes in the parietal lobe (SI and neighbouring areas) of two epileptic patients. METHODS: Wide-pass short-latency and long-latency SEPs to electrical MN stimulation were recorded in two epileptic patients by stereotactically chronically implanted electrodes in the parietal lobe (SI and neighbouring areas). To study high-frequency responses (HFOs) an off-line digital filtering of depth short-latency SEPs was performed (500-800 Hz, 24 dB roll-off). Spectral analysis was performed by fast Fourier transform. RESULTS: In both patients we recorded a N20/P30 potential followed by a biphasic N50/P70 response. A little negative response in the 100 ms latency range was the last detectable wide-pass SEP in both patients. Two HFOs components (called iP1 and iP2) were detected by mere visual analysis and spectral analysis, and were supposed to be originated within the parietal cortex. CONCLUSIONS: This was the very first study that recorded wide bandpass and high frequency SEPs by electrodes, exploring both the lateral and the mesial part of the parietal lobe and particularly that of the post-central gyrus.     

Cortical somatosensory evoked potential associated with experimental chronic cord compression by epidural neoplasm in rabbits

An experimental model of spinal cord compression was developed in rabbits by epidural neoplasms which were injected anterior to the T 13 vertebral body and grew into the spinal canal through the intervertebral foramina. With this experimental model, the neurological condition of the animals was monitored using a scale and changes of somatosensory evoked potentials (SEPs) were studied to evaluate the neurophysiological effect of experimental chronic cord compression. The animals were immobilized with pancuronium bromide and artificial respiration was maintained through a tracheostomy. SEPs were recorded by silver ball electrodes which were positioned epidurally over the somatosensory cortex through small burr holes. A subcutaneous needle placed at the nose served as a reference electrode. Right hind paw was stimulated via two percutaneous needles with 0.1 msec rectangular impulses sufficiently strong to produce motor responses, ranging from 10 to 20 volt in control rabbits. Electrical stimuli were delivered at a rate of 1 Hz. The intensity of electrical stimulation was raised up to 300 volt, when no consistent SEP was observed in the rabbit with spinal neoplasm. The SEP was summated by averaging 50 successive cortical transients with the analysis time of 200 and 500 msec. The cortical SEPs in the rabbit normally consisted of a positive-negative sequence, which we labelled P1, N1, P2, N2 and so on. Early peaks, P1 and N1, were observed constantly with average latencies of 30.1 and 53.3 msec respectively in normal rabbits. The variability of amplitudes seen even in control animals made them a less useful measure of function than latencies. Normal SEPs were preserved until the animals demonstrated moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of somatosensory evoked potentials in the evaluation of the central nervous system

SEPs may be recorded over the spine and scalp to stimulation of any accessible mixed or sensory nerve in the extremities. SEP abnormalities are useful in detecting lesions in central somatosensory pathways. They do not establish a specific diagnosis, but they may suggest or support a diagnosis made on clinical grounds. They have been used particularly to detect subclinical lesions in multiple sclerosis, but their role in following the course of this disorder is unclear. SEPs have been used as a prognostic guide in patients with hemispheric stroke and in patients who are comatose following head injury or severe cerebral anoxia; in such instances, however, the SEP often adds little to what can be determined by clinical examination. Their role in the evaluation of patients with brain death is controversial. Preserved SEPs or their early return after a spinal injury suggests an incomplete lesion, and therefore a better prognosis than otherwise. SEPs have been used to minimize or prevent intraoperative neurologic complications by monitoring spinal cord function, but their role in this regard awaits adequate validation. In patients with cervical spondylosis, SEPs elicited by stimulation of a nerve in the lower extremities may be helpful in indicating which patients are liable to develop a significant cord deficit, so that surgical treatment can be considered at an early stage. SEP abnormalities have been described in a number of other neurologic contexts, but the findings may be of more academic than clinical relevance in that they help to define the extent of neuropathologic involvement without altering the management of individual patients.     

Influence of cholinergic circuitries in generation of high-frequency somatosensory evoked potentials.

OBJECTIVE: High-frequency oscillations (HFOs) evoked by upper limb stimulation reflect highly synchronised spikes generated in the somatosensory human system. Since acetylcholine produces differential modulation in subgroups of neurons, we would determine whether cholinergic drive influences HFOs. METHODS: We recorded somatosensory evoked potentials (SEPs) from 31 scalp electrodes in 7 healthy volunteers, before and after single administration of rivastigmine, an inhibitor of central acetylcholinesterase. Right median nerve SEPs have been analysed after digital narrow bandpass filtering (500-700 Hz). Raw data were further submitted to Brain Electrical Source analysis (BESA) to evaluate the respective contribution of lemniscal, thalamic and cortical sources. Lastly, we analysed by Fast Fourier transform spectral changes after drug administration in the 10-30 ms latency range. RESULTS: Rivastigmine administration caused a significant increase of HFOs in the 18-28 ms latency range. Wavelets occurring before the onset latency of the conventional N20 SEP did not show any significant change. A similar increase concerned the strength of cortical dipolar sources in our BESA model. Lastly, we found a significant power increase of the frequency peak at about 600 Hz in P3-F3 traces after drug intake. CONCLUSIONS: Our findings demonstrate that the cortical component of HFOs is significantly enhanced by cholinergic activation. Pyramidal chattering cells, which are capable to discharge high-frequency bursts, are mainly modulated by cholinergic inputs; by contrast, acetylcholine does not modify the firing rate of fast-spiking GABAergic interneurons. We thus discuss the hypothesis that cortical HFOs are mainly generated by specialised pyramidal cells.     

Occurrence of thalamic high frequency oscillations in patients with different tremor syndromes

Objective

To assess whether high frequency oscillations (HFOs, >150?Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus.

Somatosensory evoked potentials in patients with selective impairment of position sense versus vibration sense

Ten patients with selective impairment of either position sense or vibration sense were studied with somatosensory evoked potential (SEP). Five patients with spinal cord lesion (three with MS, one with spinal cord tumor and one with spinal cord injury) lost the vibration sense below the iliac crests without impairment of the position sense. However, five patients with cerebral vascular lesions involving thalamus unilaterally showed severe impairment of position sense, though there was no asymmetry as to the vibration sense. In all these cases with spinal and cerebral lesions, SEPs showed abnormalities in the distributions where the position sense was impaired and were not related to the impairment of vibration sense. Our study indicates that SEP is much better correlated with the position sense than with the vibration sense at any lesion level.     

Median nerve somatosensory evoked potentials and their high-frequency oscillations in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate sensory cortical changes in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) and their high-frequency oscillation potentials. METHODS: Subjects were 15 healthy volunteers and 26 ALS patients. Median nerve SEPs were recorded and several peaks of oscillations were obtained by digitally filtering raw SEPs. The patients were sorted into three groups according to the level of weakness of abductor pollicis brevis muscle (APB): mild, moderate and severe. The latencies and amplitudes of main and oscillation components of SEP were compared among normal subjects and the three patient groups. RESULTS: The early cortical response was enlarged in the moderate weakness group, while it was attenuated in the severe weakness group. No differences were noted in the size ratios of oscillations to the main SEP component between the patients and normal subjects. The central sensory conduction time (CCT) and N20 duration were prolonged in spite of normal other latencies. CONCLUSIONS: The median nerve SEP amplitude changes are associated with motor disturbances in ALS. The cortical potential enhancement of SEPs with moderate weakness in ALS may reflect some compensatory function of the sensory cortex for motor disturbances. SIGNIFICANCE: The sensory cortical compensation for motor disturbances is shown in ALS, which must be important information for rehabilitation.     

Correlation between the analgesic effect by thalamic relay nucleus stimulation and somatosensory evoked potentials recorded from thalamus]

Electric stimulation of the thalamic sensory relay nucleus (Vc) has an analgesic effect on deafferentation pain, however, the analgesic effect differs from patient to patient. Electrode position and state of the substrate stimulated are considered important factors influencing the analgesic effect. In order to determine the best position for the stimulating electrodes, we recorded somatosensory evoked potentials (SEPs) from stimulating electrodes implanted in the Vc and compared thalamic SEPs with the analgesic effect of Vc stimulation. The subjects were thirteen patients with deafferentation pain, four patients with thalamic lesions, seven patients with suprathalamic lesions and two patients with infrathalamic lesions. We inserted the electrode array into the Vc stereotactically, and fixed it so that stimulation-induced paresthesia would cover the painful frea. The electrode array consisted of the four contact points of four electrodes spaced at 2 mm intervals within 10 mm from the tip. Using bipolar combinations of the four electrodes (twelve combinations in all), we stimulated the Vc for about half an hour with each combination. We then rated the degree (%) of analgesia as 100% when pain disappeared and 0% when there was no change. Thalamic SEPs elicited after stimulation of the contralateral median nerve were recorded from all four contact points simultaneously. The latencies, amplitudes and recorded positions of large early positive components (P1) followed by large negative components (N1) with latencies between 10 and 20 msec were then analyzed and compared with the best electrode combination for optimal pain relief and with the degree of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrathalamic non-propagating generators of high-frequency (1000 Hz) somatosensory evoked potential (SEP) bursts recorded subcortically in man.

OBJECTIVES: Recently, bursts of high-frequency (1000 Hz) median nerve somatosensory evoked potential (SEP) wavelets were recorded subcortically near and inside the thalamus from deep brain electrodes implanted for tremor therapy. This study aimed to clarify whether these subcortical SEP bursts reflect evoked axonal volleys running in the thalamocortical radiation or a locally restricted intrathalamic response.METHODS: During deep brain electrode implantation, median nerve SEP were recorded in 7 patients sequentially along the subcortical stereotactic trajectory at sites +20 and +10 mm above the respective target nucleus (ventral intermediate thalamus or nucleus subthalamicus). Low- and high-frequency SEP components (corner frequency 430 Hz) were analyzed separately with respect to peak latency and amplitude as they changed along the recording trajectory.RESULTS: Individual wavelets of the subcortical 1000 Hz SEP burst showed fixed peak latencies independent from the depth of the electrode penetration; they increased markedly in amplitude with decreasing distance to the thalamus. In contrast, the amplitude gradient between the two recording sites was shallower for the low-frequency SEP component, which peaked earlier at the lower recording site.CONCLUSIONS: Subcortically recorded 1000 Hz SEP wavelet bursts predominantly reflect locally restricted near-field activity, presumably generated in the somatosensory relay nucleus. In contrast, the variable peak latency of the subcortical low-frequency component could reflect postsynaptic potentials sequentially evoked during passage of the lemniscal afferences curving through the thalamus and contributions from the thalamocortical radiation.     

Cortical somatosensory evoked potentials in spinal cord injury patients.

The amplitude and latency of somatosensory evoked potentials (SEPs) in healthy subjects depend on intensity of stimulation. The effect of this parameter on SEPs in patients with neurologic disorders has not been systematically studied, although it could have a profound impact if SEPs are to be used for prognostication. We have compared the latency and amplitude of SEPs in healthy subjects and patients with spinal cord injury (SCI). Stimulation intensity was standardized at two different biologically calibrated levels. Cortical SEPs in patients with SCI showed greater decrease in latency and increase in amplitude with increased intensity of stimulation in comparison to healthy subjects. These phenomena were observed in the majority of patients with incomplete SCI who subsequently showed improvement in cortical SEPs. We observed situations in which the SEP was absent with the usual intensity of stimulation and present only with the stronger stimulation intensity. Furthermore, SEP latencies often changed dramatically with different intensities of stimulation, potentially making any calculation of central conduction velocity meaningless without precise standardization of stimulation. These findings demonstrate a necessity for a biological calibration of stimulation intensity to improve the repeatability of SEPs. We suggest the use of two different standardized intensities of stimulation for SEP studies in SCI patients, one of which should be stronger than the intensity presently recommended.     

Somatosensory evoked responses to dermatomal stimulation in cervical spinal cord injured and normal subjects

This exploratory study investigates dermatomal evoked potential patterns in the upper extremities of normal and spinal cord injured subjects. Fifteen normal subjects without neurologic deficits and twelve patients with partial or complete spinal cord injuries were tested at dermatomal levels C5, C6, C7, C8, and T1, and also at median and ulnar nerve sites. Responses were recorded at the scalp. Analyses of evoked response patterns included measurement and comparison of peak and interpeak latencies and amplitudes as well as blind ratings of the degree of abnormality of evoked potential waveforms. Analyses were also made of relationships between evoked potential data and neurological findings on clinical examination. There appeared to be a fairly consistent SEP response among normals when dermatomes C6 through C8 are stimulated. Less consistent responses are observed when C5 and T1 are stimulated. In general, spinal cord injured subjects as compared to normal subjects had evoked responses with less consistent peaks, more amplitude diminution, and greater diffuseness and overall pattern abnormality even at dermatomal levels that were intact on clinical neurologic examination. There was also a distinct progression of overall SEP abnormality in dermatomes with impaired vibration, light touch, and position sense. There were no consistent differences in interpeak latencies between SEPs of normal and spinal cord injured subjects at intact dermatomes, but there were significant differences in EP abnormalities (EPA scores). Possible reasons for the differences in the SEP responses between normals and spinal cord injured subjects include spinal cord injury not detectable by clinical exam. Difficulty in obtaining objective and accurate sensory reports also contributes to data unreliability. In conclusion, we believe that stimulation of specific sensory dermatomes merits further study, as it has a number of possible clinical uses. These include: (1) surgical monitoring at more specific levels than monitoring with mixed nerve root stimulation, (2) for study of specific nerve root injury, and (3) as an aid in examining the neurological status in acutely injured spinal cord patients who are unable to cooperate adequately during examination, such as the very young or those with lowered levels of awareness associated with head injury. Additional information which could be useful to obtain is cervical dermatomal stimulation with spinal recording sites.