- Email: [email protected]
Identification and characterization of somatosensory off responses
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / b r a i n r e s
Research Report
Identification and characterization of somatosensory off responses Lynne Spackman a,⁎, Stewart Boyd a , Tony Towell b a
Department of Clinical Neurophysiology, Great Ormond Street Hospital, London, UK Department of Psychology, University of Westminster, London, UK
b
A R T I C LE I N FO
AB S T R A C T
Article history:
Event-related potentials (ERPs) have been recorded in response to the offset of sensory
Accepted 21 December 2005
stimulation in both the auditory and visual modalities. The present experiment employed
Available online 6 September 2006
vibratory stimulation to characterize somatosensory ERPs in response to different duration stimuli. In two separate experiments, we recorded attended and unattended somatosensory
Keywords:
ERPs to 70 Hz, sine wave stimuli using the following durations: 20 ms, 50 ms, 70 ms, 150 ms,
Somatosensory
170 ms, 250 ms and 1000 ms. An oscillating coil delivered stimuli through a ‘T-bar’ to digits 2
Evoked potential
and 3 of the right hand. The amplitude and latency measurements of P50, P100 and a later
On response
negative component (No1) were analyzed using MANOVA. There was no significant
Off response
difference in the latency values of the P50 and P100, but as the duration increased, there
Sustained potential
was a significant increase (P < 0.01) in the latency of No1. No1 appeared 130 ms ± 9 ms following the offset of the stimulus. Amplitude values of the P50 and P100 components decreased as the stimulus duration increased and this effect became significant (P < 0.05) as the duration difference increased. Stimuli of 150 ms or greater evoked a negative baseline shift that persisted for the duration of the stimulus and area measurements in 7 out of the 10 subjects showed a significant increase in amplitude when the stimulus was attended. An intracranial case study supported these findings. The characteristics of the No1 component indicate it is a somatosensory off response, and it, in conjunction with the P50 and sustained potential, may reflect activity of a neural system that is responsive to changes in the tactile environment. © 2006 Published by Elsevier B.V.
1.
Introduction
Short transient cortical responses to the onset and offset of a sensory stimulus have been reported for both the visual and auditory systems. However, the off response tends to be smaller and more difficult to obtain as it is often subsumed by earlier waveform components. It requires stimulus durations of greater than 500 ms to clearly characterize the off response in these two sensory modalities (Crevits et al., 1982;
⁎ Corresponding author. Fax: +44 207 829 8627. E-mail address: [email protected] (L. Spackman). 0006-8993/$ – see front matter © 2006 Published by Elsevier B.V. doi:10.1016/j.brainres.2005.12.135
Hari et al., 1997). In the somatosensory system, there is evidence of individual on–off neurons in the somatosensory cortex of monkeys (Sur et al., 1984), but to date, there are no reports of an off response recorded from human subjects. One possible reason may lie with the type of stimulation most commonly used in the study of somatosensory-evoked potentials (SEPs). In the somatosensory system, manipulation of the stimulus characteristics has been more limited owing to the use of
54
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
direct electrical stimulation on the nerve. The majority of previous studies have utilized electrical stimulation to evoke SEPs, and this is the most common stimulus type used clinically (for a review, see Desmedt, 1988). One advantage of using electrical stimulation is that it bypasses sensory receptors and directly stimulates afferent nerves; thus, the temporal dispersion in the afferent volleys arriving at the cortex is small, and the resulting evoked potentials are large and distinct. However, there is a lack of specificity with regard to the type of fibers activated, and in bypassing the sensory receptors with an all-or-nothing activation, there is a loss of natural discrimination. It is also more difficult to apply prolonged stimulation. In the 1980s, mechanical stimulation with rapid rise times (such as tapping and vibration) was tested (Larson and Prevec, 1970, Onofrj et al., 1999), and the early/mid latency components were shown to closely resemble those elicited by electrical stimulation, though with a somewhat later latency and lower amplitude (Hämäläinen et al., 1990). However, unlike electrical stimulation, mechanical stimulation allows for easier manipulation of the stimulus duration and provides a controlled means of stimulating distinct groups of skin mechanoreceptors (Bolanowski et al., 1988, Valbo and Johansson, 1984). For example vibrotactile stimuli above 60 Hz excite predominantly the Pacinian receptors (RAII), while low-frequency stimuli are specific for non-Pacinian receptors (RAI) (Johansson et al., 1982). Mechanical stimulation is also better tolerated than electrical stimulation and more in keeping with ‘normal’ everyday tactile stimulation. In this study, we measured somatosensory-evoked potentials to a range of stimulus durations using a high-frequency vibration applied to the fingers. We aimed to determine the presence of on–off responses similar to those reported for the auditory and visual modalities and present a case study where these potentials were recorded using intracranial subdural electrodes.
2.
Results
2.1.
Study 1
The latencies of the P50 and P100 components showed no significant difference between the different stimulus durations. However, the P50 component showed a significant difference between electrode locations (F(5,40) = 51.79 P < 0.001) with an increase in latency over the right scalp electrodes (ipsilateral to the side of stimulation). There was no significant difference in the P100 latency between electrode locations. For the amplitudes of the P50 and P100 components repeated measure analysis indicates a significant decrease in amplitude with increasing duration (F(5,40) = 15.80 P < 0.001, F(5,40) = 10.29, P < 0.001 respectively) and between electrode locations (F(5,40) = 9.68 P < 0.001, F(5,40) = 9.57 P < 0.001) on the ipsilateral vs. contralateral hemisphere. There was no significant interaction between these effects. Component amplitudes were largest over the midline and contralateral hemisphere for all stimulus durations. However, Bonferroni corrected paired-samples t tests showed a significant differ-
ence in amplitude (P < 0.05) between the P50 and P100 amplitudes of each duration except between 20 ms and 50 ms, and between 150 ms and 170 ms (Fig. 1B). For the No1 component, there was a significant difference in latency between durations (F(5,40) = 74.63, P < 0.001) (Figs. 1A and C) but no significant differences in latency between electrode locations. Repeated measures analysis also showed a significant difference in the amplitude across the different durations (F(5,40) = 16.94, P < 0.001) as well as significant differences between electrode locations (F(5,40) = 5.32, p = 0.01) in a manner similar to that of the P50 and P100 components. It peaked between 120 and 144 ms (average = 129.7 ms ± 9.1 ms) following the offset of the stimulus, with no significant difference between the different stimulus durations. The scalp distribution of this component was similar to that of the P100 component (Fig. 2A). At the longer stimulus durations (150 ms+), a positive component (labeled Po1) was observed preceding No1 by 85 ms ± 4 ms but, in several subjects, was obscured by other waveform components. At the shorter durations, this component was not readily observable, most likely being subsumed by the P100 or N130 components. At the longer durations, the waveform did not reach the baseline between the end of the P100/N130 components and the start of the Po1/No1 complex, rather there was a negative baseline shift that lasted throughout the duration of the stimulus. This phenomenon appeared maximally over the left centro-parietal region (Fig. 2B). The presence of a similar shift in the responses to the shorter durations is suggested by the broadening of the P50/P100 complex observed when comparing the responses to 20-ms, 50-ms and 70-ms stimulus durations (Fig. 1A). This may reflect a sustained potential similar to that reported in the auditory and visual systems (Picton et al., 1978a; Noda et al., 1998; Huettel et al., 2004). In order to examine the possible effects of habituation or anticipation on the resulting waveforms, the grand average responses to the first and one hundredth stimulus were compared. There was no difference in the morphology or distribution of the responses. However, the response to the first stimulus did show a primacy effect, with the amplitude of the P50, P100 and No1 components being significantly higher (P < 0.05), and there was a clear P300 component that was not present in the later response. When the grand average response to the one hundredth stimulus was compared to that of the one hundred and fiftieth, there was no significant difference in latency, amplitude, scalp distribution or morphology.
2.2.
Study 2
A series of waveforms similar to that described above was observed. The increase to a 1000-ms duration stimuli showed a clearer sustained potential, and there was a significant decrease in amplitude values of the P50/P100 components when compared to those obtained in the previous experiment (P < 0.01). This followed the trend observed in study 1, i.e., as the duration of the stimuli increased the amplitude of the P50 and P100 components decreased. The negative baseline shift observed at the shorter durations became more prominent
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
55
Fig. 1 – Study 1. (A) Different stimulus durations at C1. Note the increase in latency of the large positive component (No1). (B) Shows the difference between the component amplitudes with different duration stimuli. (C) Shows the difference between the component latencies with different duration stimuli.
using the 1000-ms stimulus. It often shifted the Po1/No2 complex negative to baseline and appeared to persist for the duration of the stimulus. It had a scalp distribution different from the transient on–off responses, appearing maximally over C3 and CCP3. This was confirmed by comparing the maximum area values for the 170 ms (between 160 and 270 ms) and 250 ms (between 160 and 366 ms) responses. These durations were chosen as they discount the effects of the N130 and Po1 responses, which tend to have similar distributions.
2.2.1.
Attended vs. unattended conditions
The results obtained from the runs in which the subject had to attend the stimuli show a similar waveform morphology to those previously described with the addition of a clear N250/ P300 complex in response to the target stimuli. In general, the responses obtained in the attended condition appear slightly earlier and higher in amplitude (Fig. 3). The decrease in latency was only significance for the P50/P100components (P < 0.05). The increase in amplitude reached significance for P50/P100, N130 and No1 components (P < 0.05) for the shorter durations; however, the No 1 amplitude increase was not found to be significant for stimulus durations of 170 and
250 ms. The N130 amplitude enhancement was particularly notable in the responses obtained using 170 ms and 250 ms (Fig. 3). In 7 out of the 10 subjects tested in the attend/ignore condition, there was a significant increase (P < 0.05) in the area values of the 170-ms and 250-ms responses in the attended condition, suggesting that there was also an increase in the amplitude of the sustained response with attention.
2.3.
Study 3
The ERP waveforms recorded from the subdural grid may be seen in Figs. 4A and B. They consisted of a small negative deflection at 46–54 ms followed by a large positive deflection at 75–80 ms; these appeared to phase reverse over the postcentral sulcus. This was immediately followed by a large negative component, which appears to increase slightly in latency as the duration of the stimulus increased. At a stimulus duration of 20 ms, the latency was 148 ms, at 250 ms, it was 164 ms, and at 1000 ms, it was 175 ms. A similar component was seen from the scalp recordings but was not as well defined. A negatively shifted sustained component was then seen, recorded from the contacts
56
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
Fig. 2 – Schematic of the scalp distribution of the grand average responses. (A) Results from experiment 1, with the 20-ms and 250-ms duration responses overlaid. (B) Results from experiment 2, 1000-ms stimulus duration responses.
straddling the post-central gyrus. This component was most clearly seen using the 1000 ms. No shift was readily apparent when using the 20-ms stimulus. Following this shift at
250- and 1000-ms stimulus durations was a small negative deflection followed by a large positive deflection which was most notable over the superior part of the grid, on the
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
57
Fig. 3 – Study 2. Comparison of attended and ignored SSEP responses to nontarget stimuli at C1.
contacts covering the rostral section of the post-central gyrus.
3.
Discussion
On and off responses have been reported for both the visual and auditory system, so it is not unexpected that similar duration dependent responses would be present in the somatosensory system; however, it would be remiss to assume that this is the case or to assume that these responses behave in the same manner. Rudimentary characterization of these responses needs to be done in order to predicate how they may change or interact within the manipulation of somatosensory stimuli and subsequent cognitive processing. This study examines the transient on response, and the previously uncharacterized off response and sustained potential, in the somatosensory system when using mechanical stimulation of the median nerve. The somatosensory on response consists of the N35-P50/ P100 complex and the somatosensory off response has a small positive deflection (Po1) followed by a larger negative deflection (No1). The Po1 component of the responses to stimulus durations under 150 ms was not readily detectable. While we cannot discount possible masking or gating effects that may be inhibiting the generators of the Po1 component, it is most like that it is imbedded within other components, such as the P100 or N130, in a manner similar to the short duration off-set responses observed in the auditory system (Hillyard and Picton, 1978). The later, No1 component of the off response may clearly be seen to significantly increase in latency as the stimulus duration increases (Fig. 1) but appears an average of 130 ms after the cessation of the stimulus; this is independent
of stimulus duration. The distribution of the off response is very similar to that of the on response, appearing maximally over the contralateral parietal region, with phase reversal over the central–parietal areas. Also seen was a significant decrease in the amplitude of the P50/P100 components with increasing stimulus duration but there was no significant change in the No1 amplitude. A similar phenomenon in the auditory system was reported by Hillyard and Picton (1978) who found that as tone bursts were made longer but onset asynchrony was fixed, then the N1/P2 onset response became smaller, and the N1/P1 offset response became larger. This interaction between the two responses indicates that they are not physiologically independent processes. More recent work has shown that the N1 and P1 on and off components are generated in overlapping cortical regions, and the auditory ‘off’ response is generated primarily by a group of neurons that are topographically near, but slightly more anterior, to those generating the ‘on’ response. However, these differences are very small and in some cases do not reach significance (Noda et al., 1998, Pantev et al., 1996). In the somatosensory system, cellular recordings have found rapidly adapting neuronal populations that respond either to the onset or offset of a stimulus or to both (Sur et al., 1984). Taken together, this evidence suggests that the somatosensory transient onset and offset responses may also have separate generators and that the similar scalp distribution of the on and off responses seen in this study does not preclude the possibility of separate, but closely adjoining neuronal populations. The 70-Hz vibratory stimulus used in this study preferentially stimulates the Pacinian corpuscles which project bilaterally to the SII area of the somatosensory cortex (Ferrington and Rowe, 1980 and Maldjian et al., 1999) and
58
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
Fig. 4 – Study 3. (A) 20-ms and 250-ms vibratory somatosensory responses recorded from subdural contacts in study 3. (B) 1000-ms vibratory somatosensory responses recorded from subdural contacts in study 3.
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
Fig. 5 – MRI reconstruction showing the placement of the subdural contacts used in study 3.
SSEPs recorded from the scalp show a larger, more distinct P100 response than is seen with other forms of mechanical stimulation (Hämäläinen et al., 1990), which is one of the advantages of using this type of stimulation. In this study, the on response is a complex of the P50 and P100 components, often with a more pronounced P100. These components are thought to arise from SI and SII cortices respectively (Hämäläinen et al., 1990), and it is possible, even probable, that the off response we recorded is similarly a complex of components reflecting activation of different cortical areas. The contralateral emphasis of these responses seen in this study may reflect the contribution of the lateralized P50 (SI) responses, and more precise stimulation may be able to separate the P50 and P100 responses, and there may even be a difference between SI and SII on and off responses. Further study may reveal similar processes taking place in higher order somatosensory areas such as Brodmann area 40. Also observed was a sustained-potential following the P100 component where the waveform approaches but does not come back down to baseline before the off response appears. This is similar to the sustained-field response to long duration stimuli reported in the auditory and visual systems (Crevits et al., 1982, Hari et al., 1997, Picton et al., 1978b). In the auditory system, this potential has been shown to be distinct from the contingent negative variation (CNV) (Picton et al., 1978b) and is seen using stimulus durations over 600 ms. It had a distribution different from that of the on and off responses, being more lateral and anterior, but still showed a clear emphasis over the hemisphere contralateral to the side of stimulation. As this distribution is different from the P50 and P100 components, it is possible that the cortical generators may arise in an area separate from the SI or SII regions. Cellular recordings in area 3b of owl and macaque monkeys have found a group of slowly adapting neurons that respond not only to the onset and offset of a stimulus but also respond throughout the duration of the stimulus. These are located only in the middle layers of the cortex, with a slightly different distribution from those cells responding only to the onset or offset of the stimulus (Sur et al., 1984). This sustained-field is most clearly seen at the longest stimulus durations used, 170 ms, 250 ms and 1000 ms for both the intracranial and scalp recordings. The onset of this
59
potential at the scalp is between 130 and 165 ms, which is comparable to the 120–180 ms onset reported for the auditory sustained potential (Picton et al., 1978b, Pantev et al., 1996) and considerably earlier than the latencies reported for the CNV (>400 ms) (Rebert and Knott, 1970). It was recorded in both the attended and unattended experimental conditions, which also makes it unlikely to be the CNV. Attention to the somatosensory stimuli can enhance the amplitude of the scalp recorded transient and sustained responses. In the task given attention was required throughout the duration of the stimuli in order to discriminate changes in the stimulus duration. The increase in the amplitude of the sustained response under these conditions may reflect an actual increase in the sensory sustainedpotential, but the possibility of an added CNV associated with temporal uncertainty cannot be ruled out. The increase in amplitude and decrease in latency of the transient on and off responses are similar to those reported for other sensory modalities. While it is early to comment on the clinical or prognostic value of these findings, it is likely that pathologies affecting the somatosensory system will disrupt these components, possibly in a specific manner. By characterizing the normal presentation of the on and off response, abnormalities in the system will be more readily apparent, and this may aid in further diagnosing and characterizing certain disease processes. The general similarity between the late evoked potential responses in the primary sensory cortices may reflect a common basis that enables further cognitive processing and sensory integration. Further study examining other parameters, such as varying the ISI, frequency or intensity of the stimulus, would help to further characterize these responses. This would lead to a more thorough understanding of how the somatosensory responses are similar, and different, to those of the other modalities; providing the necessary foundation in understanding how different sensory information is integrated and how the differing temporal development of these sensory responses may underlie some of the cognitive changes that are seen in human development.
4.
Experimental procedure
4.1.
Subjects
4.1.1.
Study 1 and 2
A group of 10 subjects participated in the experiment (study 1: ages 22–36 years, 6 males; study 2: ages 19–40 years, 5 males), and all were right-handed as measured using the short form of the Edinburgh Handedness test (Oldfield, 1971). All subjects were healthy, with no self-reported history of psychiatric disorders, neurological disorders, or of injury to the central or peripheral nervous system. Informed consent was obtained from each subject, and the study was approved by the Great Ormond Street Hospital for Children/Institute of Child Health Research Ethics Committee.
4.1.2.
Study 3
A child with a prefrontal tumor and resultant refractory epilepsy was undergoing presurgical invasive monitoring to
60
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
assess the epileptogenic zone and areas of functional cortex were studied. This was done with hospital ethical approval and parental consent. The patient was an otherwise normal 14-year-old girl with seizure onset at 8 years of age. She has had multiple seizure types, but her most common manifestations are spasm like movements with an ongoing indescribable feeling that often have a right side emphasis. Consciousness is preserved during these events. Magnetic resonance imaging (MRI) showed a lesion over the left prefrontal region. A subdural platinum electrode array with 20 contacts was placed over the left sensory/motor strips and 2 6-contact electrode strips were placed over the lateral frontal cortex (Fig. 5). None of the contacts were placed over the lesion owing to significant surgical risks at the time of implantation. Before surgical implantation, a MRI scan was taken and was used to construct a three dimensional image of the patient's skull and cortex. This 3D computer image was then coregistered to the patient's skull by obtaining a number of scalp co-ordinates using the Image Guidance System (IGS). A postsurgical computerized tomography scan was obtained showing the placement of the contacts against the skull. Using the IGS, the 3D position of individual contacts were obtained and superimposed on the 3D reconstruction of the cortex. This confirmed the location of the contacts on the cortex.
4.1.3.
Stimuli
The stimuli consisted of 70 Hz sine wave vibratory bursts of variable duration. In study 1, stimulus durations of 20 ms, 50 ms, 70 ms, 150 ms, 170 ms or 250 ms were presented. In study 2, the stimulus duration was increased to 1000 ms in the unattended condition. In the attended condition stimulus durations of 20 ms, 70 ms, 150 ms and 250 ms were used. In study 3, only the 20-ms, 250-ms and 1000-ms stimulus durations were presented. The stimuli were delivered via a ‘T-bar’ attached to an oscillating coil. The coil was driven by a computer generated 70-Hz sine wave, which had a consistent T-bar displacement of ±1.9 V. The force variations arising from varying contact pressure on the T-bar were monitored using an impedance head located between the T-bar and oscillating coil. Control studies showed that normal variations in contact pressure were not sufficiently large to significantly affect the
cortical responses. The oscillating coil was at the zero phase point at the stimulus onset, always rising in the positive direction. This facilitated the synchronous activation of fibers in the fingertips and minimizes ‘jitter’ of the cortical-evoked potentials.
4.1.4.
SEP recordings
In studies 1 and 2, 45 Ag/AgCl electrodes were applied based on a modified version of the International 10–10 system and with the highest density over the central third of the scalp. During the recording, the reference was placed at POz and the ground at FPz. The subjects were tested in a single recording session lasting 2 h with a 10-min break in the middle. Each recording session included 6 runs consisting of 500 vibratory stimuli delivered with a fixed stimulus onset asynchrony of 1 s, and there was a minimum of 2 min between each run. The order of presentation of each block was randomized for each subject. During the recordings, subjects sat in a comfortable chair with their arm and wrist supported and asked to watch a self-chosen video placed 1.5 m away. The video was used to draw the subjects' attention away from the stimuli, to minimize eye movements and was set at sufficient volume to mask any noise made by the oscillating coil of the stimulator. The subject's forearm, wrist and palm were supported in a padded armrest with the distal phalanx of digits 2 and 3 resting gently on the T-bar. Subjects were monitored to ensure that only these fingers rested on the T-bar, and that there was minimal joint movement. Stimulation of these two digits was used as it selectively stimulates the median nerve. The stimuli were delivered only to the right hand in order to minimize the length of the recording session. In study 2, 2 runs were performed using the same set-up as described above, but with longer stimulus duration than those used in experiment 1. In addition, 4 attended runs were performed in which the patient was asked to fixate on a dot in front of them and to count the number of deviant stimuli (a clearly detectable change in duration). The stimuli were the same as those used in experiment 1, and each block was presented in a random order and counter balanced. White noise was administered through head phones to mask any sound from the oscillator.
Table 1 – Mean ± SD peak component latencies and amplitudes Stimulus duration (ms) 20 50 70 150 170 250 1000
μVms Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat
P50 2.64 72.8 2.47 72.6 2.63 72.4 2.17 72.8 1.59 71.0 1.78 73.4 0.78 76.3
± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.96 3.0 0.80 4.7 0.83 2.6 0.76 4.9 0.55 4.7 0.33 4.6 0.44 5.6
The label n/a indicates the component could not be reliably measured.
P100 1.78 93.2 2.18 92.2 2.48 93.0 1.61 93.4 1.83 94.2 1.84 94.2 n/a n/a
± ± ± ± ± ± ± ± ± ± ± ±
0.69 5.0 0.98 5.4 0.77 4.6 0.95 5.0 0.82 5.7 0.60 6.3
Po1 n/a n/a n/a n/a n/a n/a n/a n/a 0.99 175.1 1.05 248.3 0.90 1069.4
± ± ± ± ± ±
0.69 15.1 0.51 17.8 0.0.70 18.2
No1 1.57 178.9 1.76 183.2 1.83 197.2 1.05 306.7 1.43 298.2 1.13 380.2 1.82 1204.5
± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.78 5.9 0.80 5.6 0.77 8.7 0.75 17.7 0.72 10.3 0.49 12.0 1.0 16.0
61
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
Table 2 – Attended vs. ignored mean ± SD peak component latencies and amplitudes μV ms
Stimulus duration (ms) 20
IGN ATT
70
IGN ATT
170
IGN ATT
250
IGN ATT
Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat
P50 2.33 74.4 2.52 69.8 2.11 72.5 2.01 71.6 1.66 73.6 1.86 70.2 1.63 74.1 1.71 72.4
In study 3, intracranial recordings were collected from most subdural contacts. However, recordings could not be obtained from G001, and G002, owing to an excess of 50Hz interference. The reference and ground were placed at SA02 and SA01 respectively (Fig. 5). The recording session lasted about 1 h and was performed on the telemetry ward, with the patient sitting up in bed watching a video. Stimulation was applied to the fingers of the right hand with hand and wrist supported by pillows.
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.83 2.8 0.58 3.3 0.84 3.9 0.63 4.1 0.48 3.2 0.46 4.0 0.68 4.0 0.62 4.3
P100 1.84 92.2 1.97 90.8 1.94 94.0 2.04 92.3 1.90 96.2 1.72 95.1 1.44 96.7 1.20 95.4
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.95 4.9 0.89 5.4 0.77 4.3 0.76 4.0 0.66 3.8 0.66 4.8 0.51 8.0 0.48 6.1
N130 0.49 130 0.89 130.5 1.44 126.5 1.36 128.7 1.19 129.8 1.30 128.9 1.30 133.3 1.44 133.9
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.33 6.5 0.64 5.8 0.77 3.1 0.71 4.2 0.46 4.5 0.49 4.9 0.49 2.3 0.63 6.1
No1 1.12 168.2 1.74 185.1 1.29 183.7 1.76 185.4 1.20 280.7 1.41 281.9 1.32 360.4 1.32 364.4
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.61 11.8 0.69 15.9 0.54 14.5 0.83 15.1 0.47 20.4 0.51 9.7 0.36 19.3 0.42 23.9
Amplitude and latency measurements were taken from electrodes P7, P8, C1, Cz, C2, FC1, FCz and FC2 (Table 1) and analyzed using MANOVA. Bonferroni analysis was performed post hoc. Similar analysis was performed for the attended and unattended responses separately (Table 2), and then the amplitudes and latencies were compared across the two conditions.
REFERENCES
4.1.5.
Analysis
Continuous EEG data were collected using ‘SYNAMPS’ amplifiers set to amplify at ×12500 with a bandpass of 0.05–200 Hz and a sampling rate of 500 Hz. The continuous data were analyzed further offline as outlined below. In each study, the data were also re-montaged using a global field power reference in order to minimize the possible effects of using a POz acquisition reference. In studies 1 and 3, epochs of −50 to 600 ms were constructed using Neuroscan 4.2 software. The epochs were baseline corrected using the average voltage calculated between −50 ms and −10 ms prestimulus and digitally filtered between 1 and 40 Hz. Automatic artefact rejection of ±75 μV was performed based on all channels then the epochs were averaged. For each subject two averages were obtained and compared to ensure replicability before inclusion in the grand average. In study 2, epochs of −50 to 1600 ms (longer duration stimuli) and −50 to 600 ms (attended condition stimuli) were similarly constructed as outlined above. The averaged evoked potentials consisted of a sequence of peaks, N35-P50-N70-P100-N130-N200-Po1-No1 and were recorded between the fronto-central and left parietal regions, with phase reversal over the centro-parietal area (Fig. 2A). Only the P50, P100 and No1 peaks were analyzed for all stimulus durations, as these were of primary interest in the study. However, at the longer durations, a small positive component, Po1, was observed preceding No1, and the values for this component were included in the analysis for the stimulus durations over 170 ms. Peak latency and amplitude values for these components are outlined in Table 1.
Bolanowski, S.J., Gesheider, G.A., Verillo, R.T., Checkowsky, C.M., 1988. Four channels mediate the mechanical aspect of touch. J. Acoust. Soc. Am. 84, 1680–1694. Crevits, L., vanLith, G., Viifvinkel-Bruinenga, S., 1982. On and off contribution to the combined occipital on–off response to a pattern stimulus. Ophthalmologica 184 (3), 169–173. Desmedt, J.E., 1988. Somatosensory evoked potentials. In: Picton, T.W. (Ed.), Human Event-related Potentials. Elsevier Science Publishers B.V. (Biomedical Division), Amsterdam–New York–Oxford, pp. 245–360. Ferrington, D.G., Rowe, M., 1980. Differential contribution to coding of cutaneous vibratory information by cortical somatosensory areas I and II. J. Neurophysiol. 43 (2), 310–331. Hämäläinen, H., Kekoni, J., Mikko, S., Reinikainen, K., Näätänen, R., 1990. Human somatosensory evoked potentials to mechanical pulses and vibration: contribution of SI and SII somatosensory cortices to P50 and P100 components. Electroencephalogr. Clin. Neurophysiol. 75, 13–21. Hari, R., Pelizzone, M., Makela, J.P., Hallstrom, J., Leinonen, L., Lounasm, O.V., 1997. Neuromagnetic responses of the human auditory cortex to on–offsets of noise bursts. Audiology 26 (1), 31–43. Hillyard, S.A., Picton, T.W., 1978. On and off components in the auditory evoked potential. Percept. Psychophys. 24, 391–398. Huettel, S.A., McKeown, M.J., Hart, S., Allison, T., Song, A.W., Spencer, D.D., McCarthy, G., 2004. Linking hemodynamic and electrophysiological measures of brain activity: evidence from functional MRI and Intracranial field potentials. Cereb. Cortex 14, 165–173. Johansson, R.S., Landström, U., Lundström, R., 1982. Responses of mechanoreceptive afferent units in the glabrous skin of the human hand to sinusoidal skin displacements. Brain Res. 244, 17–25. Larson, L.E., Prevec, T.S., 1970. Somatosensory response to
62
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
mechanical stimulation as recorded in human EEG. Electroencephalogr. Clin. Neurophysiol. 28, 162–172. Maldjian, J.A., Gottschalk, A., Patel, R.S., Detre, J.A., Alsop, D.C., 1999. The somatosensory somatotopic map of the human hand demonstrated at 4 Tesla. NeuroImage 10 (1), 55–62. Noda, K., Tonoike, M., Doi, K., Koizuka, I., Yamaguchi, M., Seo, R., Matsumoto, N., Teruhisa, N., Takeda, N., Kubo, T., 1998. Auditory evoked off-response: its source distribution is different from that of on-response. NeuroReport 9 (11), 2621–2625. Oldfield, R.C., 1971. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113. Onofrj, M., Basciani, M., Fulgente, T., Bazzano, S., Malatesta, G., Curatola, L., 1999. Maps of somatosensory evoked potentials (SEPs) to mechanical (tapping) stimuli: comparison with P14, N20, P22, N30 of electrically elicited SEPs. Electroencephalogr. Clin. Neurophysiol. 77, 314–319. Pantev, C., Eulitz, C., Hamson, S., Ross, B., Roberts, L.E., 1996. The auditory evoked “Off” response: sources and comparison with
the “On” and the “Sustained” responses. Ear Hear. 17 (3), 255–265. Picton, T.W., Woods, D.L., Proulx, G.B., 1978a. Human auditory sustained potentials: I. The nature of the response. Electroencephalogr. Clin. Neurophysiol. 45, 186–197. Picton, T.W., Woods, D.L., Proulx, G.B., 1978b. Human auditory sustained potentials: II. Stimulus relationships. Electroencephalogr. Clin. Neurophysiol. 45, 198–210. Rebert, C.S., Knott, J.R., 1970. The vertex non-specific evoked potential and latency of the contingent negative variation. Electroencephalogr. Clin. Neurophysiol. 28, 561–565. Sur, M., Wall, J.T., Kaas, J.H., 1984. Modular distribution of neurons with slowly adapting and rapidly adapting responses in area 3b of somatosensory cortex in monkeys. J. Neurophysiol. 51 (4), 724–744. Valbo, Å.B., Johansson, R.S., 1984. Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum. Neurobiol. 3, 3–14.
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / b r a i n r e s
Research Report
Identification and characterization of somatosensory off responses Lynne Spackman a,⁎, Stewart Boyd a , Tony Towell b a
Department of Clinical Neurophysiology, Great Ormond Street Hospital, London, UK Department of Psychology, University of Westminster, London, UK
b
A R T I C LE I N FO
AB S T R A C T
Article history:
Event-related potentials (ERPs) have been recorded in response to the offset of sensory
Accepted 21 December 2005
stimulation in both the auditory and visual modalities. The present experiment employed
Available online 6 September 2006
vibratory stimulation to characterize somatosensory ERPs in response to different duration stimuli. In two separate experiments, we recorded attended and unattended somatosensory
Keywords:
ERPs to 70 Hz, sine wave stimuli using the following durations: 20 ms, 50 ms, 70 ms, 150 ms,
Somatosensory
170 ms, 250 ms and 1000 ms. An oscillating coil delivered stimuli through a ‘T-bar’ to digits 2
Evoked potential
and 3 of the right hand. The amplitude and latency measurements of P50, P100 and a later
On response
negative component (No1) were analyzed using MANOVA. There was no significant
Off response
difference in the latency values of the P50 and P100, but as the duration increased, there
Sustained potential
was a significant increase (P < 0.01) in the latency of No1. No1 appeared 130 ms ± 9 ms following the offset of the stimulus. Amplitude values of the P50 and P100 components decreased as the stimulus duration increased and this effect became significant (P < 0.05) as the duration difference increased. Stimuli of 150 ms or greater evoked a negative baseline shift that persisted for the duration of the stimulus and area measurements in 7 out of the 10 subjects showed a significant increase in amplitude when the stimulus was attended. An intracranial case study supported these findings. The characteristics of the No1 component indicate it is a somatosensory off response, and it, in conjunction with the P50 and sustained potential, may reflect activity of a neural system that is responsive to changes in the tactile environment. © 2006 Published by Elsevier B.V.
1.
Introduction
Short transient cortical responses to the onset and offset of a sensory stimulus have been reported for both the visual and auditory systems. However, the off response tends to be smaller and more difficult to obtain as it is often subsumed by earlier waveform components. It requires stimulus durations of greater than 500 ms to clearly characterize the off response in these two sensory modalities (Crevits et al., 1982;
⁎ Corresponding author. Fax: +44 207 829 8627. E-mail address: [email protected] (L. Spackman). 0006-8993/$ – see front matter © 2006 Published by Elsevier B.V. doi:10.1016/j.brainres.2005.12.135
Hari et al., 1997). In the somatosensory system, there is evidence of individual on–off neurons in the somatosensory cortex of monkeys (Sur et al., 1984), but to date, there are no reports of an off response recorded from human subjects. One possible reason may lie with the type of stimulation most commonly used in the study of somatosensory-evoked potentials (SEPs). In the somatosensory system, manipulation of the stimulus characteristics has been more limited owing to the use of
54
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
direct electrical stimulation on the nerve. The majority of previous studies have utilized electrical stimulation to evoke SEPs, and this is the most common stimulus type used clinically (for a review, see Desmedt, 1988). One advantage of using electrical stimulation is that it bypasses sensory receptors and directly stimulates afferent nerves; thus, the temporal dispersion in the afferent volleys arriving at the cortex is small, and the resulting evoked potentials are large and distinct. However, there is a lack of specificity with regard to the type of fibers activated, and in bypassing the sensory receptors with an all-or-nothing activation, there is a loss of natural discrimination. It is also more difficult to apply prolonged stimulation. In the 1980s, mechanical stimulation with rapid rise times (such as tapping and vibration) was tested (Larson and Prevec, 1970, Onofrj et al., 1999), and the early/mid latency components were shown to closely resemble those elicited by electrical stimulation, though with a somewhat later latency and lower amplitude (Hämäläinen et al., 1990). However, unlike electrical stimulation, mechanical stimulation allows for easier manipulation of the stimulus duration and provides a controlled means of stimulating distinct groups of skin mechanoreceptors (Bolanowski et al., 1988, Valbo and Johansson, 1984). For example vibrotactile stimuli above 60 Hz excite predominantly the Pacinian receptors (RAII), while low-frequency stimuli are specific for non-Pacinian receptors (RAI) (Johansson et al., 1982). Mechanical stimulation is also better tolerated than electrical stimulation and more in keeping with ‘normal’ everyday tactile stimulation. In this study, we measured somatosensory-evoked potentials to a range of stimulus durations using a high-frequency vibration applied to the fingers. We aimed to determine the presence of on–off responses similar to those reported for the auditory and visual modalities and present a case study where these potentials were recorded using intracranial subdural electrodes.
2.
Results
2.1.
Study 1
The latencies of the P50 and P100 components showed no significant difference between the different stimulus durations. However, the P50 component showed a significant difference between electrode locations (F(5,40) = 51.79 P < 0.001) with an increase in latency over the right scalp electrodes (ipsilateral to the side of stimulation). There was no significant difference in the P100 latency between electrode locations. For the amplitudes of the P50 and P100 components repeated measure analysis indicates a significant decrease in amplitude with increasing duration (F(5,40) = 15.80 P < 0.001, F(5,40) = 10.29, P < 0.001 respectively) and between electrode locations (F(5,40) = 9.68 P < 0.001, F(5,40) = 9.57 P < 0.001) on the ipsilateral vs. contralateral hemisphere. There was no significant interaction between these effects. Component amplitudes were largest over the midline and contralateral hemisphere for all stimulus durations. However, Bonferroni corrected paired-samples t tests showed a significant differ-
ence in amplitude (P < 0.05) between the P50 and P100 amplitudes of each duration except between 20 ms and 50 ms, and between 150 ms and 170 ms (Fig. 1B). For the No1 component, there was a significant difference in latency between durations (F(5,40) = 74.63, P < 0.001) (Figs. 1A and C) but no significant differences in latency between electrode locations. Repeated measures analysis also showed a significant difference in the amplitude across the different durations (F(5,40) = 16.94, P < 0.001) as well as significant differences between electrode locations (F(5,40) = 5.32, p = 0.01) in a manner similar to that of the P50 and P100 components. It peaked between 120 and 144 ms (average = 129.7 ms ± 9.1 ms) following the offset of the stimulus, with no significant difference between the different stimulus durations. The scalp distribution of this component was similar to that of the P100 component (Fig. 2A). At the longer stimulus durations (150 ms+), a positive component (labeled Po1) was observed preceding No1 by 85 ms ± 4 ms but, in several subjects, was obscured by other waveform components. At the shorter durations, this component was not readily observable, most likely being subsumed by the P100 or N130 components. At the longer durations, the waveform did not reach the baseline between the end of the P100/N130 components and the start of the Po1/No1 complex, rather there was a negative baseline shift that lasted throughout the duration of the stimulus. This phenomenon appeared maximally over the left centro-parietal region (Fig. 2B). The presence of a similar shift in the responses to the shorter durations is suggested by the broadening of the P50/P100 complex observed when comparing the responses to 20-ms, 50-ms and 70-ms stimulus durations (Fig. 1A). This may reflect a sustained potential similar to that reported in the auditory and visual systems (Picton et al., 1978a; Noda et al., 1998; Huettel et al., 2004). In order to examine the possible effects of habituation or anticipation on the resulting waveforms, the grand average responses to the first and one hundredth stimulus were compared. There was no difference in the morphology or distribution of the responses. However, the response to the first stimulus did show a primacy effect, with the amplitude of the P50, P100 and No1 components being significantly higher (P < 0.05), and there was a clear P300 component that was not present in the later response. When the grand average response to the one hundredth stimulus was compared to that of the one hundred and fiftieth, there was no significant difference in latency, amplitude, scalp distribution or morphology.
2.2.
Study 2
A series of waveforms similar to that described above was observed. The increase to a 1000-ms duration stimuli showed a clearer sustained potential, and there was a significant decrease in amplitude values of the P50/P100 components when compared to those obtained in the previous experiment (P < 0.01). This followed the trend observed in study 1, i.e., as the duration of the stimuli increased the amplitude of the P50 and P100 components decreased. The negative baseline shift observed at the shorter durations became more prominent
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
55
Fig. 1 – Study 1. (A) Different stimulus durations at C1. Note the increase in latency of the large positive component (No1). (B) Shows the difference between the component amplitudes with different duration stimuli. (C) Shows the difference between the component latencies with different duration stimuli.
using the 1000-ms stimulus. It often shifted the Po1/No2 complex negative to baseline and appeared to persist for the duration of the stimulus. It had a scalp distribution different from the transient on–off responses, appearing maximally over C3 and CCP3. This was confirmed by comparing the maximum area values for the 170 ms (between 160 and 270 ms) and 250 ms (between 160 and 366 ms) responses. These durations were chosen as they discount the effects of the N130 and Po1 responses, which tend to have similar distributions.
2.2.1.
Attended vs. unattended conditions
The results obtained from the runs in which the subject had to attend the stimuli show a similar waveform morphology to those previously described with the addition of a clear N250/ P300 complex in response to the target stimuli. In general, the responses obtained in the attended condition appear slightly earlier and higher in amplitude (Fig. 3). The decrease in latency was only significance for the P50/P100components (P < 0.05). The increase in amplitude reached significance for P50/P100, N130 and No1 components (P < 0.05) for the shorter durations; however, the No 1 amplitude increase was not found to be significant for stimulus durations of 170 and
250 ms. The N130 amplitude enhancement was particularly notable in the responses obtained using 170 ms and 250 ms (Fig. 3). In 7 out of the 10 subjects tested in the attend/ignore condition, there was a significant increase (P < 0.05) in the area values of the 170-ms and 250-ms responses in the attended condition, suggesting that there was also an increase in the amplitude of the sustained response with attention.
2.3.
Study 3
The ERP waveforms recorded from the subdural grid may be seen in Figs. 4A and B. They consisted of a small negative deflection at 46–54 ms followed by a large positive deflection at 75–80 ms; these appeared to phase reverse over the postcentral sulcus. This was immediately followed by a large negative component, which appears to increase slightly in latency as the duration of the stimulus increased. At a stimulus duration of 20 ms, the latency was 148 ms, at 250 ms, it was 164 ms, and at 1000 ms, it was 175 ms. A similar component was seen from the scalp recordings but was not as well defined. A negatively shifted sustained component was then seen, recorded from the contacts
56
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
Fig. 2 – Schematic of the scalp distribution of the grand average responses. (A) Results from experiment 1, with the 20-ms and 250-ms duration responses overlaid. (B) Results from experiment 2, 1000-ms stimulus duration responses.
straddling the post-central gyrus. This component was most clearly seen using the 1000 ms. No shift was readily apparent when using the 20-ms stimulus. Following this shift at
250- and 1000-ms stimulus durations was a small negative deflection followed by a large positive deflection which was most notable over the superior part of the grid, on the
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
57
Fig. 3 – Study 2. Comparison of attended and ignored SSEP responses to nontarget stimuli at C1.
contacts covering the rostral section of the post-central gyrus.
3.
Discussion
On and off responses have been reported for both the visual and auditory system, so it is not unexpected that similar duration dependent responses would be present in the somatosensory system; however, it would be remiss to assume that this is the case or to assume that these responses behave in the same manner. Rudimentary characterization of these responses needs to be done in order to predicate how they may change or interact within the manipulation of somatosensory stimuli and subsequent cognitive processing. This study examines the transient on response, and the previously uncharacterized off response and sustained potential, in the somatosensory system when using mechanical stimulation of the median nerve. The somatosensory on response consists of the N35-P50/ P100 complex and the somatosensory off response has a small positive deflection (Po1) followed by a larger negative deflection (No1). The Po1 component of the responses to stimulus durations under 150 ms was not readily detectable. While we cannot discount possible masking or gating effects that may be inhibiting the generators of the Po1 component, it is most like that it is imbedded within other components, such as the P100 or N130, in a manner similar to the short duration off-set responses observed in the auditory system (Hillyard and Picton, 1978). The later, No1 component of the off response may clearly be seen to significantly increase in latency as the stimulus duration increases (Fig. 1) but appears an average of 130 ms after the cessation of the stimulus; this is independent
of stimulus duration. The distribution of the off response is very similar to that of the on response, appearing maximally over the contralateral parietal region, with phase reversal over the central–parietal areas. Also seen was a significant decrease in the amplitude of the P50/P100 components with increasing stimulus duration but there was no significant change in the No1 amplitude. A similar phenomenon in the auditory system was reported by Hillyard and Picton (1978) who found that as tone bursts were made longer but onset asynchrony was fixed, then the N1/P2 onset response became smaller, and the N1/P1 offset response became larger. This interaction between the two responses indicates that they are not physiologically independent processes. More recent work has shown that the N1 and P1 on and off components are generated in overlapping cortical regions, and the auditory ‘off’ response is generated primarily by a group of neurons that are topographically near, but slightly more anterior, to those generating the ‘on’ response. However, these differences are very small and in some cases do not reach significance (Noda et al., 1998, Pantev et al., 1996). In the somatosensory system, cellular recordings have found rapidly adapting neuronal populations that respond either to the onset or offset of a stimulus or to both (Sur et al., 1984). Taken together, this evidence suggests that the somatosensory transient onset and offset responses may also have separate generators and that the similar scalp distribution of the on and off responses seen in this study does not preclude the possibility of separate, but closely adjoining neuronal populations. The 70-Hz vibratory stimulus used in this study preferentially stimulates the Pacinian corpuscles which project bilaterally to the SII area of the somatosensory cortex (Ferrington and Rowe, 1980 and Maldjian et al., 1999) and
58
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
Fig. 4 – Study 3. (A) 20-ms and 250-ms vibratory somatosensory responses recorded from subdural contacts in study 3. (B) 1000-ms vibratory somatosensory responses recorded from subdural contacts in study 3.
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
Fig. 5 – MRI reconstruction showing the placement of the subdural contacts used in study 3.
SSEPs recorded from the scalp show a larger, more distinct P100 response than is seen with other forms of mechanical stimulation (Hämäläinen et al., 1990), which is one of the advantages of using this type of stimulation. In this study, the on response is a complex of the P50 and P100 components, often with a more pronounced P100. These components are thought to arise from SI and SII cortices respectively (Hämäläinen et al., 1990), and it is possible, even probable, that the off response we recorded is similarly a complex of components reflecting activation of different cortical areas. The contralateral emphasis of these responses seen in this study may reflect the contribution of the lateralized P50 (SI) responses, and more precise stimulation may be able to separate the P50 and P100 responses, and there may even be a difference between SI and SII on and off responses. Further study may reveal similar processes taking place in higher order somatosensory areas such as Brodmann area 40. Also observed was a sustained-potential following the P100 component where the waveform approaches but does not come back down to baseline before the off response appears. This is similar to the sustained-field response to long duration stimuli reported in the auditory and visual systems (Crevits et al., 1982, Hari et al., 1997, Picton et al., 1978b). In the auditory system, this potential has been shown to be distinct from the contingent negative variation (CNV) (Picton et al., 1978b) and is seen using stimulus durations over 600 ms. It had a distribution different from that of the on and off responses, being more lateral and anterior, but still showed a clear emphasis over the hemisphere contralateral to the side of stimulation. As this distribution is different from the P50 and P100 components, it is possible that the cortical generators may arise in an area separate from the SI or SII regions. Cellular recordings in area 3b of owl and macaque monkeys have found a group of slowly adapting neurons that respond not only to the onset and offset of a stimulus but also respond throughout the duration of the stimulus. These are located only in the middle layers of the cortex, with a slightly different distribution from those cells responding only to the onset or offset of the stimulus (Sur et al., 1984). This sustained-field is most clearly seen at the longest stimulus durations used, 170 ms, 250 ms and 1000 ms for both the intracranial and scalp recordings. The onset of this
59
potential at the scalp is between 130 and 165 ms, which is comparable to the 120–180 ms onset reported for the auditory sustained potential (Picton et al., 1978b, Pantev et al., 1996) and considerably earlier than the latencies reported for the CNV (>400 ms) (Rebert and Knott, 1970). It was recorded in both the attended and unattended experimental conditions, which also makes it unlikely to be the CNV. Attention to the somatosensory stimuli can enhance the amplitude of the scalp recorded transient and sustained responses. In the task given attention was required throughout the duration of the stimuli in order to discriminate changes in the stimulus duration. The increase in the amplitude of the sustained response under these conditions may reflect an actual increase in the sensory sustainedpotential, but the possibility of an added CNV associated with temporal uncertainty cannot be ruled out. The increase in amplitude and decrease in latency of the transient on and off responses are similar to those reported for other sensory modalities. While it is early to comment on the clinical or prognostic value of these findings, it is likely that pathologies affecting the somatosensory system will disrupt these components, possibly in a specific manner. By characterizing the normal presentation of the on and off response, abnormalities in the system will be more readily apparent, and this may aid in further diagnosing and characterizing certain disease processes. The general similarity between the late evoked potential responses in the primary sensory cortices may reflect a common basis that enables further cognitive processing and sensory integration. Further study examining other parameters, such as varying the ISI, frequency or intensity of the stimulus, would help to further characterize these responses. This would lead to a more thorough understanding of how the somatosensory responses are similar, and different, to those of the other modalities; providing the necessary foundation in understanding how different sensory information is integrated and how the differing temporal development of these sensory responses may underlie some of the cognitive changes that are seen in human development.
4.
Experimental procedure
4.1.
Subjects
4.1.1.
Study 1 and 2
A group of 10 subjects participated in the experiment (study 1: ages 22–36 years, 6 males; study 2: ages 19–40 years, 5 males), and all were right-handed as measured using the short form of the Edinburgh Handedness test (Oldfield, 1971). All subjects were healthy, with no self-reported history of psychiatric disorders, neurological disorders, or of injury to the central or peripheral nervous system. Informed consent was obtained from each subject, and the study was approved by the Great Ormond Street Hospital for Children/Institute of Child Health Research Ethics Committee.
4.1.2.
Study 3
A child with a prefrontal tumor and resultant refractory epilepsy was undergoing presurgical invasive monitoring to
60
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
assess the epileptogenic zone and areas of functional cortex were studied. This was done with hospital ethical approval and parental consent. The patient was an otherwise normal 14-year-old girl with seizure onset at 8 years of age. She has had multiple seizure types, but her most common manifestations are spasm like movements with an ongoing indescribable feeling that often have a right side emphasis. Consciousness is preserved during these events. Magnetic resonance imaging (MRI) showed a lesion over the left prefrontal region. A subdural platinum electrode array with 20 contacts was placed over the left sensory/motor strips and 2 6-contact electrode strips were placed over the lateral frontal cortex (Fig. 5). None of the contacts were placed over the lesion owing to significant surgical risks at the time of implantation. Before surgical implantation, a MRI scan was taken and was used to construct a three dimensional image of the patient's skull and cortex. This 3D computer image was then coregistered to the patient's skull by obtaining a number of scalp co-ordinates using the Image Guidance System (IGS). A postsurgical computerized tomography scan was obtained showing the placement of the contacts against the skull. Using the IGS, the 3D position of individual contacts were obtained and superimposed on the 3D reconstruction of the cortex. This confirmed the location of the contacts on the cortex.
4.1.3.
Stimuli
The stimuli consisted of 70 Hz sine wave vibratory bursts of variable duration. In study 1, stimulus durations of 20 ms, 50 ms, 70 ms, 150 ms, 170 ms or 250 ms were presented. In study 2, the stimulus duration was increased to 1000 ms in the unattended condition. In the attended condition stimulus durations of 20 ms, 70 ms, 150 ms and 250 ms were used. In study 3, only the 20-ms, 250-ms and 1000-ms stimulus durations were presented. The stimuli were delivered via a ‘T-bar’ attached to an oscillating coil. The coil was driven by a computer generated 70-Hz sine wave, which had a consistent T-bar displacement of ±1.9 V. The force variations arising from varying contact pressure on the T-bar were monitored using an impedance head located between the T-bar and oscillating coil. Control studies showed that normal variations in contact pressure were not sufficiently large to significantly affect the
cortical responses. The oscillating coil was at the zero phase point at the stimulus onset, always rising in the positive direction. This facilitated the synchronous activation of fibers in the fingertips and minimizes ‘jitter’ of the cortical-evoked potentials.
4.1.4.
SEP recordings
In studies 1 and 2, 45 Ag/AgCl electrodes were applied based on a modified version of the International 10–10 system and with the highest density over the central third of the scalp. During the recording, the reference was placed at POz and the ground at FPz. The subjects were tested in a single recording session lasting 2 h with a 10-min break in the middle. Each recording session included 6 runs consisting of 500 vibratory stimuli delivered with a fixed stimulus onset asynchrony of 1 s, and there was a minimum of 2 min between each run. The order of presentation of each block was randomized for each subject. During the recordings, subjects sat in a comfortable chair with their arm and wrist supported and asked to watch a self-chosen video placed 1.5 m away. The video was used to draw the subjects' attention away from the stimuli, to minimize eye movements and was set at sufficient volume to mask any noise made by the oscillating coil of the stimulator. The subject's forearm, wrist and palm were supported in a padded armrest with the distal phalanx of digits 2 and 3 resting gently on the T-bar. Subjects were monitored to ensure that only these fingers rested on the T-bar, and that there was minimal joint movement. Stimulation of these two digits was used as it selectively stimulates the median nerve. The stimuli were delivered only to the right hand in order to minimize the length of the recording session. In study 2, 2 runs were performed using the same set-up as described above, but with longer stimulus duration than those used in experiment 1. In addition, 4 attended runs were performed in which the patient was asked to fixate on a dot in front of them and to count the number of deviant stimuli (a clearly detectable change in duration). The stimuli were the same as those used in experiment 1, and each block was presented in a random order and counter balanced. White noise was administered through head phones to mask any sound from the oscillator.
Table 1 – Mean ± SD peak component latencies and amplitudes Stimulus duration (ms) 20 50 70 150 170 250 1000
μVms Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat
P50 2.64 72.8 2.47 72.6 2.63 72.4 2.17 72.8 1.59 71.0 1.78 73.4 0.78 76.3
± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.96 3.0 0.80 4.7 0.83 2.6 0.76 4.9 0.55 4.7 0.33 4.6 0.44 5.6
The label n/a indicates the component could not be reliably measured.
P100 1.78 93.2 2.18 92.2 2.48 93.0 1.61 93.4 1.83 94.2 1.84 94.2 n/a n/a
± ± ± ± ± ± ± ± ± ± ± ±
0.69 5.0 0.98 5.4 0.77 4.6 0.95 5.0 0.82 5.7 0.60 6.3
Po1 n/a n/a n/a n/a n/a n/a n/a n/a 0.99 175.1 1.05 248.3 0.90 1069.4
± ± ± ± ± ±
0.69 15.1 0.51 17.8 0.0.70 18.2
No1 1.57 178.9 1.76 183.2 1.83 197.2 1.05 306.7 1.43 298.2 1.13 380.2 1.82 1204.5
± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.78 5.9 0.80 5.6 0.77 8.7 0.75 17.7 0.72 10.3 0.49 12.0 1.0 16.0
61
BR A IN RE S E A RCH 1 1 14 ( 20 0 6 ) 5 3 –6 2
Table 2 – Attended vs. ignored mean ± SD peak component latencies and amplitudes μV ms
Stimulus duration (ms) 20
IGN ATT
70
IGN ATT
170
IGN ATT
250
IGN ATT
Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat Amp Lat
P50 2.33 74.4 2.52 69.8 2.11 72.5 2.01 71.6 1.66 73.6 1.86 70.2 1.63 74.1 1.71 72.4
In study 3, intracranial recordings were collected from most subdural contacts. However, recordings could not be obtained from G001, and G002, owing to an excess of 50Hz interference. The reference and ground were placed at SA02 and SA01 respectively (Fig. 5). The recording session lasted about 1 h and was performed on the telemetry ward, with the patient sitting up in bed watching a video. Stimulation was applied to the fingers of the right hand with hand and wrist supported by pillows.
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.83 2.8 0.58 3.3 0.84 3.9 0.63 4.1 0.48 3.2 0.46 4.0 0.68 4.0 0.62 4.3
P100 1.84 92.2 1.97 90.8 1.94 94.0 2.04 92.3 1.90 96.2 1.72 95.1 1.44 96.7 1.20 95.4
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.95 4.9 0.89 5.4 0.77 4.3 0.76 4.0 0.66 3.8 0.66 4.8 0.51 8.0 0.48 6.1
N130 0.49 130 0.89 130.5 1.44 126.5 1.36 128.7 1.19 129.8 1.30 128.9 1.30 133.3 1.44 133.9
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.33 6.5 0.64 5.8 0.77 3.1 0.71 4.2 0.46 4.5 0.49 4.9 0.49 2.3 0.63 6.1
No1 1.12 168.2 1.74 185.1 1.29 183.7 1.76 185.4 1.20 280.7 1.41 281.9 1.32 360.4 1.32 364.4
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
0.61 11.8 0.69 15.9 0.54 14.5 0.83 15.1 0.47 20.4 0.51 9.7 0.36 19.3 0.42 23.9
Amplitude and latency measurements were taken from electrodes P7, P8, C1, Cz, C2, FC1, FCz and FC2 (Table 1) and analyzed using MANOVA. Bonferroni analysis was performed post hoc. Similar analysis was performed for the attended and unattended responses separately (Table 2), and then the amplitudes and latencies were compared across the two conditions.
REFERENCES
4.1.5.
Analysis
Continuous EEG data were collected using ‘SYNAMPS’ amplifiers set to amplify at ×12500 with a bandpass of 0.05–200 Hz and a sampling rate of 500 Hz. The continuous data were analyzed further offline as outlined below. In each study, the data were also re-montaged using a global field power reference in order to minimize the possible effects of using a POz acquisition reference. In studies 1 and 3, epochs of −50 to 600 ms were constructed using Neuroscan 4.2 software. The epochs were baseline corrected using the average voltage calculated between −50 ms and −10 ms prestimulus and digitally filtered between 1 and 40 Hz. Automatic artefact rejection of ±75 μV was performed based on all channels then the epochs were averaged. For each subject two averages were obtained and compared to ensure replicability before inclusion in the grand average. In study 2, epochs of −50 to 1600 ms (longer duration stimuli) and −50 to 600 ms (attended condition stimuli) were similarly constructed as outlined above. The averaged evoked potentials consisted of a sequence of peaks, N35-P50-N70-P100-N130-N200-Po1-No1 and were recorded between the fronto-central and left parietal regions, with phase reversal over the centro-parietal area (Fig. 2A). Only the P50, P100 and No1 peaks were analyzed for all stimulus durations, as these were of primary interest in the study. However, at the longer durations, a small positive component, Po1, was observed preceding No1, and the values for this component were included in the analysis for the stimulus durations over 170 ms. Peak latency and amplitude values for these components are outlined in Table 1.
Bolanowski, S.J., Gesheider, G.A., Verillo, R.T., Checkowsky, C.M., 1988. Four channels mediate the mechanical aspect of touch. J. Acoust. Soc. Am. 84, 1680–1694. Crevits, L., vanLith, G., Viifvinkel-Bruinenga, S., 1982. On and off contribution to the combined occipital on–off response to a pattern stimulus. Ophthalmologica 184 (3), 169–173. Desmedt, J.E., 1988. Somatosensory evoked potentials. In: Picton, T.W. (Ed.), Human Event-related Potentials. Elsevier Science Publishers B.V. (Biomedical Division), Amsterdam–New York–Oxford, pp. 245–360. Ferrington, D.G., Rowe, M., 1980. Differential contribution to coding of cutaneous vibratory information by cortical somatosensory areas I and II. J. Neurophysiol. 43 (2), 310–331. Hämäläinen, H., Kekoni, J., Mikko, S., Reinikainen, K., Näätänen, R., 1990. Human somatosensory evoked potentials to mechanical pulses and vibration: contribution of SI and SII somatosensory cortices to P50 and P100 components. Electroencephalogr. Clin. Neurophysiol. 75, 13–21. Hari, R., Pelizzone, M., Makela, J.P., Hallstrom, J., Leinonen, L., Lounasm, O.V., 1997. Neuromagnetic responses of the human auditory cortex to on–offsets of noise bursts. Audiology 26 (1), 31–43. Hillyard, S.A., Picton, T.W., 1978. On and off components in the auditory evoked potential. Percept. Psychophys. 24, 391–398. Huettel, S.A., McKeown, M.J., Hart, S., Allison, T., Song, A.W., Spencer, D.D., McCarthy, G., 2004. Linking hemodynamic and electrophysiological measures of brain activity: evidence from functional MRI and Intracranial field potentials. Cereb. Cortex 14, 165–173. Johansson, R.S., Landström, U., Lundström, R., 1982. Responses of mechanoreceptive afferent units in the glabrous skin of the human hand to sinusoidal skin displacements. Brain Res. 244, 17–25. Larson, L.E., Prevec, T.S., 1970. Somatosensory response to
62
BR A IN RE S EA RCH 1 1 14 ( 20 0 6 ) 5 3 –62
mechanical stimulation as recorded in human EEG. Electroencephalogr. Clin. Neurophysiol. 28, 162–172. Maldjian, J.A., Gottschalk, A., Patel, R.S., Detre, J.A., Alsop, D.C., 1999. The somatosensory somatotopic map of the human hand demonstrated at 4 Tesla. NeuroImage 10 (1), 55–62. Noda, K., Tonoike, M., Doi, K., Koizuka, I., Yamaguchi, M., Seo, R., Matsumoto, N., Teruhisa, N., Takeda, N., Kubo, T., 1998. Auditory evoked off-response: its source distribution is different from that of on-response. NeuroReport 9 (11), 2621–2625. Oldfield, R.C., 1971. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113. Onofrj, M., Basciani, M., Fulgente, T., Bazzano, S., Malatesta, G., Curatola, L., 1999. Maps of somatosensory evoked potentials (SEPs) to mechanical (tapping) stimuli: comparison with P14, N20, P22, N30 of electrically elicited SEPs. Electroencephalogr. Clin. Neurophysiol. 77, 314–319. Pantev, C., Eulitz, C., Hamson, S., Ross, B., Roberts, L.E., 1996. The auditory evoked “Off” response: sources and comparison with
the “On” and the “Sustained” responses. Ear Hear. 17 (3), 255–265. Picton, T.W., Woods, D.L., Proulx, G.B., 1978a. Human auditory sustained potentials: I. The nature of the response. Electroencephalogr. Clin. Neurophysiol. 45, 186–197. Picton, T.W., Woods, D.L., Proulx, G.B., 1978b. Human auditory sustained potentials: II. Stimulus relationships. Electroencephalogr. Clin. Neurophysiol. 45, 198–210. Rebert, C.S., Knott, J.R., 1970. The vertex non-specific evoked potential and latency of the contingent negative variation. Electroencephalogr. Clin. Neurophysiol. 28, 561–565. Sur, M., Wall, J.T., Kaas, J.H., 1984. Modular distribution of neurons with slowly adapting and rapidly adapting responses in area 3b of somatosensory cortex in monkeys. J. Neurophysiol. 51 (4), 724–744. Valbo, Å.B., Johansson, R.S., 1984. Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum. Neurobiol. 3, 3–14.