ORIGINAL RESEARCH
Occipital Lobe Lesions Result in a Displacement of Magnetoencephalography Visual Evoked Field Dipoles Elizabeth W. Pang,*† Bill H. W. Chu,* and Hiroshi Otsubo*†
Purpose: The pattern-reversal visual evoked potential measured electrically from scalp electrodes is known to be decreased, or absent, in patients with occipital lobe lesions. We questioned whether the measurement and source analysis of the neuromagnetic visual evoked field (VEF) might offer additional information regarding visual cortex relative to the occipital lesion. Methods: We retrospectively examined 12 children (6–18 years) with occipital lesions on MRI, who underwent magnetoencephalography and ophthalmology as part of their presurgical assessment. Binocular half-field pattern-reversal VEFs were obtained in a 151-channel whole-head magnetoencephalography. Data were averaged and dipole source analyses were performed for each half-field stimulation. Results: A significant lateral shift (P , 0.02) in the dipole location was observed in the lesional hemisphere compared with those in the nonlesional hemisphere, regardless of the lesion location. No differences were observed in latency, strength (moment), and residual errors of VEF dipoles between the lesional and nonlesional hemispheres. Conclusions: Magnetoencephalography demonstrated the mass effect on the dipole location of VEF in children with occipital lesions. Magnetoencephalography may be useful as a screening test of visual function in young patients. We discuss potential explanations for this lateral shift and emphasize the utility of adding the magnetoencephalography pattern-reversal visual evoked field protocol to the neurologic work-up. Key Words: Magnetoencephalography, Pattern-reversal visual evoked potentials, Occipital lobe lesions, Pediatric. (J Clin Neurophysiol 2014;31: 456–461)
T
he pattern-reversal visual evoked potential (PRVEP), with stimulus presentation to each visual hemifield and measured with a minimum of three occipital electrodes, is used in the clinical setting to assess the integrity of the visual pathway (American Encephalographic Society, 1994). There is consensus that the PRVEP is a reliable and sensitive tool in the diagnosis of anterior visual pathway lesions, whereby PRVEP amplitude attenuations are typically correlated with compressive lesions of the anterior visual pathways while PRVEP latency delays are typically correlated with demyelinating lesions (Aminoff and Goodin, 1994; Chiappa and Hill, 1997). The applicability of the PRVEP to retrochiasmic lesions is less clear. In an early study, all 20 adult patients with occipital lobe abnormalities showed some form of VEP abnormality, although a consistent pattern was not identifiable (Streletz et al., 1981). However, full-field stimulation was used, which precluded the
From the *Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada; and †Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada. Address correspondence and reprint requests to Elizabeth W. Pang, PhD, Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail: [email protected]. Copyright Ó 2014 by the American Clinical Neurophysiology Society
ISSN: 0736-0258/14/3105-0456
456
examination of each occipital hemisphere. In other studies using hemifield stimulation, adults with retrochiasmic lesions showed amplitude effects. One reported that amplitude asymmetry was the most sensitive measure, particularly if the amplitude of the affected hemisphere was ,1 mV and normal in the unaffected hemisphere (Kuroiwa and Celesia, 1981), and the other reported attenuated or absent responses in the affected hemisphere (Blumhardt et al., 1982). Despite these findings of amplitude effects in retrochiasmic lesions, the caveat was given that field perimetry was still a more sensitive diagnostic measure (Kuroiwa and Celesia, 1981), although a study involving 22 adults compared PRVEP findings with perimetry results found a high correlation: normal PRVEPs were associated with full and normal visual fields; abnormal or equivocal VEPs were associated with visual field defects (Holder, 1985). In the testing of pediatric patients, the PRVEP is used in nonverbal children to assess visual acuity and visual function because the normative values and testing parameters are well known (Allison et al., 1984; Fenwick et al., 1981). Since young children are poor at, or unable to, report subjective experiences of visual loss or disturbance and children often have a difficult time cooperating with the lengthy demands of perimetry, there is a clear benefit in choosing the PRVEP over field perimetry if the PRVEP is found to be accurate in the diagnosis of a posterior pathway lesion. One study reported that in six children with occipital lobe tumors, all demonstrated abnormal PRVEP with small-sized checks and half-field stimulation (Wenzel et al., 1988); however, it is not clear whether these abnormalities were in latency delays or amplitude decrements. Magnetoencephalography (MEG) is a technique that measures the endogenous neuromagnetic fluctuations from synchronous activity of the cortical pyramidal cells (Hari and Salmelin, 2012). It has been suggested that MEG recordings may offer a more sensitive measurement of the visual evoked response in situations involving occipital lobe pathology because the MEG signal is not distorted by transmission through tissues with different relative conductivities (Cuffin and Cohen, 1979). The pattern-reversal visual evoked field (PRVEF) has been well studied in healthy populations aged from 15 to 87 years (Armstrong et al., 1991). It is described as a triphasic response with components at N75m, P100m, and N145m (Barnikol et al., 2006; Hashimoto et al., 1999) with cortical sources of halffield stimulations localized to contralateral striate cortices, specifically within the calcarine fissures (Hatanaka et al., 1997; Seki et al., 1996). These sources have been confirmed with a functional MRI– constrained MEG study (Perfetti et al., 2007). Furthermore, these demonstrated a retinotopic organization (Nakamura et al., 1997) and correlated well with the electrical PRVEP (Shigeto et al., 1998). Optimal stimulation parameters have been explored (Chen et al., 2005), and clinical practice guidelines have been published (Burgess et al., 2011). The VEF response to flash stimulation has been well examined in neonates (Matuz et al., 2012). The developmental
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
trajectory and maturation of the pattern-reversal electrical VEP has been well delineated (Allison et al., 1983, 1984), and this has translated to the use of the magnetic VEF in pediatric clinical practice (Burgess et al., 2011; Chuang et al., 2006; Otsubo and Snead, 2001). However, a systematic study of development of the PRVEF in MEG across childhood has not been conducted. A study has examined the use of PRVEF in ophthalmologic deficits (Nakasato and Yoshimoto, 2000), and one study has examined the impact of occipital lesions on the PRVEF (Nakasato et al., 1996). Using full-field stimulation in 13 patients with intracranial structural lesions, this article reported a high correlation between VEF dipole localizability and visual function (Nakasato et al., 1996). There has not yet been a study using hemifield stimulation to examine the visual evoked response in each cerebral cortex separately, and there has not yet been a study examining these effects in children. We hypothesized that the PRVEF to hemifield stimulation might be useful in localizing functional visual cortex in cases of intracranial lesions. Furthermore, we queried whether MEG VEF could have future application to young children or preverbal children who may not cooperate for visual field perimetry but may cooperate for MEG testing. Therefore, we examined the pattern-reversal whole-head MEG response to hemifield stimulation in a group of children with occipital lobe lesions to determine whether there was a relationship between the lesion, visual function, and the VEF response.
VEF Displacement Due to Occipital Lobe Lesions
visual fields testing results. All subjects were seen by Neurology and Neuro-opthalmology. If patients cooperated for perimetry, these results are reported, but if patients did not cooperate, then results of visual field testing by confrontation are reported.
Pattern-Reversal Visual Evoked Field Stimuli Patients were tested with our standard clinical protocol (Sharma et al., 2007), which is consistent with the recommended MEG Clinical Practice Guidelines (Burgess et al., 2011). Stimuli consisted of a high-contrast black-and-white checkerboard pattern, which reversed at 2 Hz. The stimuli were backprojected to a screen placed 70 cm in front of the patient, and each check subtended a visual angle of 498. This large check size was chosen to ensure stimulation of the periphery and to allow for any decrements in visual acuity. Patients were tested with binocular stimulation to either left or right hemifield in sequential conditions. Subjects were instructed to fixate on a red dot on the center of the screen. Binocular stimulation was used as this is known to activate a larger cortical region than monocular stimulation, and hemifield stimulation allowed activation of one cerebral cortex at a time. The frontal MEG channels were monitored for high amplitude neuromagnetic fluctuations consistent with large eye movements and blinks. If there were a large number of blinks and eye movements that degraded the quality of the averaged VEF, an additional replication was repeated. Hundred trials were included per replication, and two replications were performed per hemifield. Testing was completed in less than 4 minutes.
METHODS Subject Selection This was a retrospective chart review. We searched the Hospital for Sick Children MEG database from 2000 to 2008 for patients with VEF testing. Of the 669 records, 48 had VEF testing. Of these 48, many had occipital lobe seizures, but we selected only those patients with MRI-identified lesions in the occipital lobe. Twelve patients met these criteria. We did not place restrictions on lesion size or type.
Subjects Twelve patients (7 boys, 5 girls; 6–18 years) were included in our study. Table 1 shows patient demographics, lesion location, and
TABLE 1.
Patients were dark adapted in the magnetically shielded room and tested supine on the MEG bed. Three MEG fiducial coils were placed on the nasion and left and right pre-auricular points to allow co-registration with anatomical MRI. Data acquisition was on the 151-channel whole-head MEG (CTF Omega; MISL; Port Coquitlam, BC, Canada) at the Hospital for Sick Children in Toronto. Data were acquired continuously at a sampling rate of 625 Hz, a bandpass of 0.1 to 100 Hz (60 Hz notch off) with the third-order gradient plus adaptive balancing noise reduction. Motion tolerance for data acquisition was ,5 mm, and all subjects complied. On completion of MEG testing, the fiducial coils were replaced by contrast markers
Patient Demographics, Lesion Location, Lesion Type, and Visual Field Results
Subject Number 1 2 3 4 5 6 7 8 9 10 11 12
Magnetoencephalography and Anatomical MRI Data Acquisition
Age (years)
Sex
Lesion Side
Lesion
Lesion Type
Visual Fields Interpretation
6 7 8 9 12 13 14 16 10 10 14 18
M M M F M M F F F M F M
Left Left Left Left Left Left Left Left Right Right Right Right
Parieto–occipital Mesial–occipital Fronto–parieto–occipital Temporo–occipital Occipital Parieto–occipital Medial–occipital Occipital Temporo–occipital Occipital Fronto–parieto–occipital Fusiform
Angioma Glioma Porencephalic cyst Angioma DNET NYD Glioma DNET Heterotopia DNET Porencephalic cyst Ganglioglioma
Normal Normal Grossly normal Normal Normal Normal Normal Normal Left homonymous hemianopsia Normal Normal Left altitudinal field defect
DNET, dysembroplastic neuroepithelial tumour.
Copyright Ó 2014 by the American Clinical Neurophysiology Society
457
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
E. W. Pang et al.
visible on MRI and a 1.5 T T1-weighted SPGR MRI (GE Signa Advantage, Milwaukee, MI) was acquired.
Magnetoencephalography Data Analysis The MRI contrast markers were coregistered with the MEG fiducial points, and individual spherical head models were created using CTF software, which fits a single-shell sphere to the extracted skull surface. Magnetoencephalography data were epoched into 0.5-second trials, which included a 0.1-second pretrigger baseline, and the data for each replication and each hemifield were separately averaged. The P100m was identified as the most prominent peak between 80 and 120 milliseconds posttrigger. Using the CTF DipoleFit module (v.4.17), one dipole was placed initially in occipital areas, and equivalent current dipoles were computed at the maximal peak amplitudes of the P100m for each hemisphere. A dipole was localized for each replication and the results were the lowest goodness-of-fit, or dipole fit error, was kept. The dipole parameters were noted for further analyses. The dipole coordinates were overlaid back onto the MRI to allow visualization of functional location relative to the lesion. Two-tailed t-tests (corrected for unequal variances) were used to compare the P100m dipole parameters between left versus right hemifield stimulations and affected versus unaffected cortical hemisphere.
RESULTS Dipole localizations for the P100m were attempted in all patients to both hemifield stimulations. In 11/12 patients, left hemifield stimulation localized to right occipital cortex, as expected. In 10/12 patients, right hemifield stimulation localized to left occipital cortex. Figure 1 shows an example of a clear P100m waveform (top) and a poorer quality, but localizable, P100m response (bottom). Figure 2 shows every location of each subject’s VEF dipoles overlaid on their own MRIs. P100m latencies were not significantly different between left hemifield (102.1 milliseconds 6 5.8 standard error of the mean [SEM]) and right hemifield (124.3 6 10.5) stimulations. Dipole fit errors also were not significantly different between left hemifield (17.1% 6 3.1 SEM) and right hemifield (23.8 6 5.4) stimulations, and dipole moments were not significantly different between left hemifield (24.0 A$m2 6 2.6 SEM) and right hemifield (25.2 6 2.6) stimulations.
Since there were no significant differences between left and right hemifield stimulations, data were regrouped into affected versus unaffected hemispheres and recompared. The dipole fit parameters for the P100m, including latency of peak, fit error, source strength (moment), and 3-dimensional coordinates, organized by affected versus unaffected hemispheres, are contained in Table 2. For the y-coordinate, negative values refer to right occipital cortex and positive to left occipital cortex. The mean and standard errors for the dependent variables submitted to statistical comparisons are contained in Table 3. Again, there were no significant differences between affected and unaffected hemisphere on measures of latency, error and moment; however, the absolute value of the y-coordinate was significantly different between the affected and unaffected hemispheres (P , 0.02). The dipoles in the affected hemisphere were displaced more laterally (2.0 units 6 0.18) compared with the dipoles in the unaffected hemisphere (1.2 units 6 0.25). X-coordinate (positive to negative: frontal to occipital) and z-coordinate (positive to negative: superior to inferior) parameters were not significantly different between the affected and unaffected hemispheres.
DISCUSSION The PRVEF was obtainable in our clinical pediatric population. As expected, left and right hemifield stimulations were equally likely to evoke a localizable P100m (92% vs. 83%, respectively) and did not demonstrate any differences in dipole latency, moment, error, or any of the other fit parameters. In contrast to the extant electrical VEP results (Blumhardt et al., 1982; Kuroiwa and Celesia, 1981), which demonstrated amplitude asymmetries between the P100 in the affected and unaffected hemispheres, the P100m in our study did not differentiate between affected and unaffected hemispheres on measures of latency, dipole moment strength or dipole fit error. However, our finding is not entirely unexpected as Holder (1985) reported that normal PRVEPs were associated with full and normal visual fields while abnormal or equivocal VEPs were associated with visual field defects, and our entire cohort, except one patient, had full and normal visual fields. Unfortunately, electrical VEPs were not performed in our study because this would have provided additional support for Holder’s (1985) assertion. Interestingly, there is a dichotomy between the goals of recording electrical versus magnetic visual evoked responses. Wenzel et al. (1988) reported abnormal PRVEP in children with
FIG. 1. Examples of the pattern-reversal visual evoked field with a clear P100m (top) and a poorer quality P100m (bottom). Tracings are averaged data from 100 trials with 151 sensors overlaid. VEF, visual evoked field; VEP, visual evoked potential. 458
Copyright Ó 2014 by the American Clinical Neurophysiology Society
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
VEF Displacement Due to Occipital Lobe Lesions
FIG. 2. Dipole fit locations for the pattern-reversal visual evoked field, for each patient, overlaid on coregistered axial MRI slices. Slices are presented in radiologic convention.
occipital lobe tumors when tested with small-sized checks. In our standard clinical MEG protocol (Sharma et al., 2007), large checks are used intentionally so as to obtain a VEF response that would meet the minimum signal-to-noise requirements for a robust dipole fit. Although it would be of interest in the future to test patients with both large and small checks, in the MEG, it is preferable to Copyright Ó 2014 by the American Clinical Neurophysiology Society
select a check size large enough to obtain an adequately clear PRVEF for dipole fitting. Because we were able to obtain dipole localizations in our cohort, our most noteworthy finding is a significant shift in the ycoordinate, whereby the dipole in the affected hemisphere demonstrated a significant lateral displacement relative to the dipole 459
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
E. W. Pang et al.
TABLE 2.
Dipole Fit Parameters for Each Patient Affected Side
Subject Number 1 2 3 4 5 6 7 8 9 10 11 12
Unaffected Side
Latency
Error
Moment
x
y
z
Latency
Error
Moment
x
y
z
d 105.6 112.0 d 96.0 150.4 161.6 81.6 121.6 142.4 86.4 84.4
d 18.13 39.35 d 8.0 7.87 15.29 20.07 26.49 38.42 20.99 20.38
d 13.69 26.09 d 22.57 39.22 35.93 21.21 21.66 25.72 23.01 8.45
d 26.8 27.4 d 28.6 25.5 25.9 26.4 25.5 24.7 26.4 28.3
d 2.8 1.9 d 2.1 2.1 1.4 1.3 22.1 22.8 21.5 22.4
d 6.1 3.4 d 2.7 4.9 5.4 4.7 7.0 3.5 6.0 4.2
102.4 107.2 118.4 96.0 97.6 d 78.4 88.0 139.2 137.6 176.0 83.2
10.56 21.65 18.07 3.39 11.11 d 3.37 14.0 61.41 27.42 32.26 7.75
36.48 13.64 20.47 24.13 21.69 d 32.93 36.27 17.24 30.93 18.13 27.48
26.8 28.1 26.6 27.4 28.4 d 26.4 25.8 25.6 26.1 24.1 27.2
20.9 21.4 21.9 21.0 20.4 d 21.0 21.3 3.2 1.3 1.0 0.3
3.8 4.8 4.5 4.3 3.4 d 4.5 4.9 4.2 3.9 7.8 5.5
location in the unaffected hemisphere. Most likely this reflects a mass effect of the lesion. This mass effect may provide an additional explanation for the presence of amplitude effects in the electrical VEP data (Blumhardt et al., 1982; Kuroiwa and Celesia, 1981) but not in our neuromagnetic data. The VEP is measured from three electrodes placed at standard fixed locations over occipital scalp. In the event that functional cortex is displaced, the electrodes are no longer situated over the functional cortex or the site of maximal response. This will be measured by the electrode as a diminished response. However, the MEG sensors acquire data over the entire occipital area, and the dipole is fit to the maximal response, even if it is displaced. It is important to point out the sparcity of development data regarding the PRVEF. While the electrical VEP has been well studied in children (Allison et al., 1984; Fenwick et al., 1981), and Armstrong et al. (1991) included an adolescent cohort in the magnetic PRVEF, to our knowledge, there has been no large-scale systematic study of the PRVEF in children using MEG. The results of this study cannot rule out the possibility that our findings are simply because of the developmental effects. As well, since our analyses were conducted within subject, and thus, a control group was not required, per se, there is a need to conduct future large-scale developmental studies in control children. Finally, a future comparison of the electrical VEP and magnetic VEF responses in the same subject, and in pediatric cohorts, would be helpful in disentangling the effects of developmental changes and neural plasticity. Our finding of a displacement in the PRVEF location in conjunction with intact visual fields suggests that function can be preserved when functional cortex is shifted but not when it is
TABLE 3.
damaged. Streletz et al. (1981) reported some form of VEF abnormality in their group of 20 patients with occipital lobe abnormalities; however, 18 of these patients had occipital infarcts. Presumably, an infarct resulted in damage to functional cortex and is therefore consistent with a VEP abnormality. In retrospect, our selection of patients with occipital lobe tumors created a very specific and homogenous patient cohort; in future, it would be of interest to examine the MEG PRVEF in other cohorts with different occipital lobe abnormalities. As well, it would be important to measure the size of the lesion and its medial/lateral extent within the occipital lobe to better understand if the PRVEP displacement is related to lesion size. However, the real value of MEG VEF results resides in its potential impact on our healthcare system by helping to triage and manage diagnostic imaging resources. For example, a young patient with visual complaints would be placed on a waiting list for a sedated MRI slot with no real indications of urgency. However, if this patient were offered an MEG and if asymmetric VEF locations were noted, this would emphasize the need to expedite the MRI, but if the VEFs were normal, then other clinical investigations should be pursued while waiting for the MRI. In summary, we have demonstrated mass effects on the dipole location of a visual evoked response in a group of children with occipital lobe tumors. This would suggest that the MEG VEF may be a diagnostic tool that is sensitive enough to identify the mass effects of a lesion on functional cortex and may be useful as a screening test before subjecting a young patient to (1) a long waiting list for an MRI and (2) an MRI done under general anesthesia. This demonstrates the added value of MEG recordings as a tool in the neurologic examination.
Comparison of P100m Dipole Parameters Between Affected and Unaffected Hemispheres
Affected side Mean 6 SEM Unaffected side Mean 6 SEM P (t-test)
n
Latency
Error
Moment
x-Coordinate
y-Coordinate (Absolute Value)
z-Coordinate
10
114.2 6 9.6
21.5 6 3.6
23.8 6 3.0
26.6 6 0.4
2.0 6 0.2
4.8 6 0.5
11
111.3 6 9.3 0.82
19.2 6 5.3 0.71
25.4 6 2.5 0.67
26.6 6 0.4 0.96
1.2 6 0.2 0.014*
4.7 6 0.4 0.85
*significant (p,0.05)
460
Copyright Ó 2014 by the American Clinical Neurophysiology Society
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
ACKNOWLEDGMENTS The authors would like to thank Rohit Sharma, Amrita Viljoen, and Stephanie Holowka for assistance with data collection and Matt J. MacDonald for editorial assistance. REFERENCES Allison T, Wood CC, Goff WR. Brain stem auditory, pattern-reversal visual, and short-latency somatosensory evoked potentials: latencies in relation to age, sex, and brain and body size. Electroencephalogr Clin Neurophysiol 1983;55:619–636. Allison T, Hume AL, Wood CC, Goff WR. Developmental and aging changes in somatosensory, auditory and visual evoked potentials. Electroencephalogr Clin Neurophysiol 1984;58:14–24. American Encephalographic Society. Guideline nine: guidelines on evoked potentials. J Clin Neurophysiol 1994;11:40–73. Aminoff MJ, Goodin DS. Visual evoked potentials. J Clin Neurophysiol 1994;11:493–499. Armstrong RA, Slaven A, Harding GF. Visual evoked magnetic fields to flash and pattern in 100 normal subjects. Vision Res 1991;31:1859–1864. Barnikol UB, Amunts K, Dammers J, et al. Pattern reversal visual evoked responses of V1/V2 and V5/MT as revealed by MEG combined with probabilistic cytoarchitectonic maps. Neuroimage 2006;31:86–108. Blumhardt LD, Barrett G, Kriss A, Halliday AM. The pattern-evoked potential in lesions of the posterior visual pathways. Ann N Y Acad Sci 1982;388:264– 289. Burgess RC, Funke ME, Bowyer SM, et al. American clinical magnetoencephalography society clinical practice guideline 2: presurgical functional brain mapping using magnetic evoked fields. J Clin Neurophysiol 2011;28(4):355–361. Chen WT, Ko YC, Liao KK, et al. Optimcal check size and reversal rate to elicit pattern-reversal MEG responses. Can J Neurol Sci 2005;32:218–224. Chiappa KH, Hill RA. Pattern-shift visual evoked potentials: interpretation. In: Chiappa KH, ed. Evoked potentials in clinical medicine. 3rd ed. Philadelphia: Lippincott-Raven, 1997: chap. 3. Chuang NA, Otsubo H, Pang EW, Chuang SH. Pediatric magnetoencephalography and magnetic source imaging. Neuroimaging Clin N Am 2006;16:193–210. Cuffin BN, Cohen D. Comparison of magnetoencephogram and electroencephalogram. Electroencephalogr Clin Neurophysiol 1979;47:132–146. Fenwick PB, Brown D, Hennesy J. The visual evoked response to pattern reversal in “normal” 6–11 year old children. Electroencephalogr Clin Neurophysiol 1981;51:49–62.
Copyright Ó 2014 by the American Clinical Neurophysiology Society
VEF Displacement Due to Occipital Lobe Lesions
Hari R, Salmelin R. Magnetoencephalography: from SQUIDs to neuroscience. Neuroimage 2012;61:386–396. Hashimoto T, Kashii S, Kikuchi M, et al. Temporal profile of visual evoked responses to pattern-reversal stimulation analyzed with a whole-head magnetometer. Exp Brain Res 1999;125:375–382. Hatanaka K, Nakasato N, Seki K, et al. Striate cortical generators of the N75, P100 and N145 components localized by pattern reversal visual evoked magnetic fields. Tohoku J Exp Med 1997;182:9–14. Holder GE. Pattern visual evoked potential in patients with posteriorly situated space-occupying lesions. Doc Ophthalmol 1985;59:121–128. Kuroiwa Y, Celesia GG. Visual evoked potentials with hemifield pattern stimulation: their use in the diagnosis of retrochiasmatic lesions. Arch Neurol 1981;38:86–90. Matuz T, Govindan RB, Preissl H, et al. Habituation of visual evoked responses in neonates and fetuses: a MEG study. Dev Cogn Neurosci 2012;2:303–316. Nakamura A, Kakigi R, Hoshiyama M, et al. Visual evoked cortical magnetic fields to pattern reversal stimulation. Brain Res Cogn Brain Res 1997;6:9–22. Nakasato N, Yoshimoto T. Somatosensory, auditory, and visual evoked magnetic fields in patients with brain diseases. J Clin Neurophysiol 2000;17:201–211. Nakasato N, Seki K, Fujita S, et al. Clinical application of visual evoked fields using an MRI-linked whole head MEG system. Front Med Biol Eng 1996;7:275–283. Otsubo H, Snead OC. Magnetoencephalography and magnetic source imaging in children. J Child Neurol 2001;16:227–235. Perfetti B, Franciotti R, Della Penna S, et al. Low- and high-frequency evoked responses following pattern reversal stimuli: a MEG study supported by fMRI constraint. Neuroimage 2007;35:1152–1167. Seki K, Nakasato N, Fujita S, et al. Neuromagnetic evidence that the P100 component of the pattern reversal visual evoked response originates in the bottom of the calcarine fissure. Electroencephalogr Clin Neurophysiol 1996;100:436–442. Sharma R, Pang EW, Mohamed I, et al. Magnetoencephalography in children: routine clinical protocol for intractable epilepsy at the Hospital for Sick Children. In: Cheyne D, Ross B, Stroink G, Weinberg H, eds. New Frontiers in Biomagnetism. 2007:685–688. (Elsevier Canada, Toronto; Intl Congress Series, vol. 1300). Shigeto H, Tobimatsu S, Yamamoto T, et al. Visual evoked cortical magnetic responses to checkerboard pattern reversal stimulation: a study on the neural generators of N75, P100 and N145. J Neurol Sci 1998;156:186–194. Streletz LJ, Bae SH, Roeshman RM, et al. Visual evoked potentials in occipital lobe lesions. Arch Neurol 1981;38:80–85. Wenzel D, Brandl U, Beck JD, et al. Visual evoked potentials in tumors from orbita to occipital lobe in childhood. Neurosurg Rev 1988;11:279–286.
461
Occipital Lobe Lesions Result in a Displacement of Magnetoencephalography Visual Evoked Field Dipoles Elizabeth W. Pang,*† Bill H. W. Chu,* and Hiroshi Otsubo*†
Purpose: The pattern-reversal visual evoked potential measured electrically from scalp electrodes is known to be decreased, or absent, in patients with occipital lobe lesions. We questioned whether the measurement and source analysis of the neuromagnetic visual evoked field (VEF) might offer additional information regarding visual cortex relative to the occipital lesion. Methods: We retrospectively examined 12 children (6–18 years) with occipital lesions on MRI, who underwent magnetoencephalography and ophthalmology as part of their presurgical assessment. Binocular half-field pattern-reversal VEFs were obtained in a 151-channel whole-head magnetoencephalography. Data were averaged and dipole source analyses were performed for each half-field stimulation. Results: A significant lateral shift (P , 0.02) in the dipole location was observed in the lesional hemisphere compared with those in the nonlesional hemisphere, regardless of the lesion location. No differences were observed in latency, strength (moment), and residual errors of VEF dipoles between the lesional and nonlesional hemispheres. Conclusions: Magnetoencephalography demonstrated the mass effect on the dipole location of VEF in children with occipital lesions. Magnetoencephalography may be useful as a screening test of visual function in young patients. We discuss potential explanations for this lateral shift and emphasize the utility of adding the magnetoencephalography pattern-reversal visual evoked field protocol to the neurologic work-up. Key Words: Magnetoencephalography, Pattern-reversal visual evoked potentials, Occipital lobe lesions, Pediatric. (J Clin Neurophysiol 2014;31: 456–461)
T
he pattern-reversal visual evoked potential (PRVEP), with stimulus presentation to each visual hemifield and measured with a minimum of three occipital electrodes, is used in the clinical setting to assess the integrity of the visual pathway (American Encephalographic Society, 1994). There is consensus that the PRVEP is a reliable and sensitive tool in the diagnosis of anterior visual pathway lesions, whereby PRVEP amplitude attenuations are typically correlated with compressive lesions of the anterior visual pathways while PRVEP latency delays are typically correlated with demyelinating lesions (Aminoff and Goodin, 1994; Chiappa and Hill, 1997). The applicability of the PRVEP to retrochiasmic lesions is less clear. In an early study, all 20 adult patients with occipital lobe abnormalities showed some form of VEP abnormality, although a consistent pattern was not identifiable (Streletz et al., 1981). However, full-field stimulation was used, which precluded the
From the *Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada; and †Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada. Address correspondence and reprint requests to Elizabeth W. Pang, PhD, Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail: [email protected]. Copyright Ó 2014 by the American Clinical Neurophysiology Society
ISSN: 0736-0258/14/3105-0456
456
examination of each occipital hemisphere. In other studies using hemifield stimulation, adults with retrochiasmic lesions showed amplitude effects. One reported that amplitude asymmetry was the most sensitive measure, particularly if the amplitude of the affected hemisphere was ,1 mV and normal in the unaffected hemisphere (Kuroiwa and Celesia, 1981), and the other reported attenuated or absent responses in the affected hemisphere (Blumhardt et al., 1982). Despite these findings of amplitude effects in retrochiasmic lesions, the caveat was given that field perimetry was still a more sensitive diagnostic measure (Kuroiwa and Celesia, 1981), although a study involving 22 adults compared PRVEP findings with perimetry results found a high correlation: normal PRVEPs were associated with full and normal visual fields; abnormal or equivocal VEPs were associated with visual field defects (Holder, 1985). In the testing of pediatric patients, the PRVEP is used in nonverbal children to assess visual acuity and visual function because the normative values and testing parameters are well known (Allison et al., 1984; Fenwick et al., 1981). Since young children are poor at, or unable to, report subjective experiences of visual loss or disturbance and children often have a difficult time cooperating with the lengthy demands of perimetry, there is a clear benefit in choosing the PRVEP over field perimetry if the PRVEP is found to be accurate in the diagnosis of a posterior pathway lesion. One study reported that in six children with occipital lobe tumors, all demonstrated abnormal PRVEP with small-sized checks and half-field stimulation (Wenzel et al., 1988); however, it is not clear whether these abnormalities were in latency delays or amplitude decrements. Magnetoencephalography (MEG) is a technique that measures the endogenous neuromagnetic fluctuations from synchronous activity of the cortical pyramidal cells (Hari and Salmelin, 2012). It has been suggested that MEG recordings may offer a more sensitive measurement of the visual evoked response in situations involving occipital lobe pathology because the MEG signal is not distorted by transmission through tissues with different relative conductivities (Cuffin and Cohen, 1979). The pattern-reversal visual evoked field (PRVEF) has been well studied in healthy populations aged from 15 to 87 years (Armstrong et al., 1991). It is described as a triphasic response with components at N75m, P100m, and N145m (Barnikol et al., 2006; Hashimoto et al., 1999) with cortical sources of halffield stimulations localized to contralateral striate cortices, specifically within the calcarine fissures (Hatanaka et al., 1997; Seki et al., 1996). These sources have been confirmed with a functional MRI– constrained MEG study (Perfetti et al., 2007). Furthermore, these demonstrated a retinotopic organization (Nakamura et al., 1997) and correlated well with the electrical PRVEP (Shigeto et al., 1998). Optimal stimulation parameters have been explored (Chen et al., 2005), and clinical practice guidelines have been published (Burgess et al., 2011). The VEF response to flash stimulation has been well examined in neonates (Matuz et al., 2012). The developmental
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
trajectory and maturation of the pattern-reversal electrical VEP has been well delineated (Allison et al., 1983, 1984), and this has translated to the use of the magnetic VEF in pediatric clinical practice (Burgess et al., 2011; Chuang et al., 2006; Otsubo and Snead, 2001). However, a systematic study of development of the PRVEF in MEG across childhood has not been conducted. A study has examined the use of PRVEF in ophthalmologic deficits (Nakasato and Yoshimoto, 2000), and one study has examined the impact of occipital lesions on the PRVEF (Nakasato et al., 1996). Using full-field stimulation in 13 patients with intracranial structural lesions, this article reported a high correlation between VEF dipole localizability and visual function (Nakasato et al., 1996). There has not yet been a study using hemifield stimulation to examine the visual evoked response in each cerebral cortex separately, and there has not yet been a study examining these effects in children. We hypothesized that the PRVEF to hemifield stimulation might be useful in localizing functional visual cortex in cases of intracranial lesions. Furthermore, we queried whether MEG VEF could have future application to young children or preverbal children who may not cooperate for visual field perimetry but may cooperate for MEG testing. Therefore, we examined the pattern-reversal whole-head MEG response to hemifield stimulation in a group of children with occipital lobe lesions to determine whether there was a relationship between the lesion, visual function, and the VEF response.
VEF Displacement Due to Occipital Lobe Lesions
visual fields testing results. All subjects were seen by Neurology and Neuro-opthalmology. If patients cooperated for perimetry, these results are reported, but if patients did not cooperate, then results of visual field testing by confrontation are reported.
Pattern-Reversal Visual Evoked Field Stimuli Patients were tested with our standard clinical protocol (Sharma et al., 2007), which is consistent with the recommended MEG Clinical Practice Guidelines (Burgess et al., 2011). Stimuli consisted of a high-contrast black-and-white checkerboard pattern, which reversed at 2 Hz. The stimuli were backprojected to a screen placed 70 cm in front of the patient, and each check subtended a visual angle of 498. This large check size was chosen to ensure stimulation of the periphery and to allow for any decrements in visual acuity. Patients were tested with binocular stimulation to either left or right hemifield in sequential conditions. Subjects were instructed to fixate on a red dot on the center of the screen. Binocular stimulation was used as this is known to activate a larger cortical region than monocular stimulation, and hemifield stimulation allowed activation of one cerebral cortex at a time. The frontal MEG channels were monitored for high amplitude neuromagnetic fluctuations consistent with large eye movements and blinks. If there were a large number of blinks and eye movements that degraded the quality of the averaged VEF, an additional replication was repeated. Hundred trials were included per replication, and two replications were performed per hemifield. Testing was completed in less than 4 minutes.
METHODS Subject Selection This was a retrospective chart review. We searched the Hospital for Sick Children MEG database from 2000 to 2008 for patients with VEF testing. Of the 669 records, 48 had VEF testing. Of these 48, many had occipital lobe seizures, but we selected only those patients with MRI-identified lesions in the occipital lobe. Twelve patients met these criteria. We did not place restrictions on lesion size or type.
Subjects Twelve patients (7 boys, 5 girls; 6–18 years) were included in our study. Table 1 shows patient demographics, lesion location, and
TABLE 1.
Patients were dark adapted in the magnetically shielded room and tested supine on the MEG bed. Three MEG fiducial coils were placed on the nasion and left and right pre-auricular points to allow co-registration with anatomical MRI. Data acquisition was on the 151-channel whole-head MEG (CTF Omega; MISL; Port Coquitlam, BC, Canada) at the Hospital for Sick Children in Toronto. Data were acquired continuously at a sampling rate of 625 Hz, a bandpass of 0.1 to 100 Hz (60 Hz notch off) with the third-order gradient plus adaptive balancing noise reduction. Motion tolerance for data acquisition was ,5 mm, and all subjects complied. On completion of MEG testing, the fiducial coils were replaced by contrast markers
Patient Demographics, Lesion Location, Lesion Type, and Visual Field Results
Subject Number 1 2 3 4 5 6 7 8 9 10 11 12
Magnetoencephalography and Anatomical MRI Data Acquisition
Age (years)
Sex
Lesion Side
Lesion
Lesion Type
Visual Fields Interpretation
6 7 8 9 12 13 14 16 10 10 14 18
M M M F M M F F F M F M
Left Left Left Left Left Left Left Left Right Right Right Right
Parieto–occipital Mesial–occipital Fronto–parieto–occipital Temporo–occipital Occipital Parieto–occipital Medial–occipital Occipital Temporo–occipital Occipital Fronto–parieto–occipital Fusiform
Angioma Glioma Porencephalic cyst Angioma DNET NYD Glioma DNET Heterotopia DNET Porencephalic cyst Ganglioglioma
Normal Normal Grossly normal Normal Normal Normal Normal Normal Left homonymous hemianopsia Normal Normal Left altitudinal field defect
DNET, dysembroplastic neuroepithelial tumour.
Copyright Ó 2014 by the American Clinical Neurophysiology Society
457
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
E. W. Pang et al.
visible on MRI and a 1.5 T T1-weighted SPGR MRI (GE Signa Advantage, Milwaukee, MI) was acquired.
Magnetoencephalography Data Analysis The MRI contrast markers were coregistered with the MEG fiducial points, and individual spherical head models were created using CTF software, which fits a single-shell sphere to the extracted skull surface. Magnetoencephalography data were epoched into 0.5-second trials, which included a 0.1-second pretrigger baseline, and the data for each replication and each hemifield were separately averaged. The P100m was identified as the most prominent peak between 80 and 120 milliseconds posttrigger. Using the CTF DipoleFit module (v.4.17), one dipole was placed initially in occipital areas, and equivalent current dipoles were computed at the maximal peak amplitudes of the P100m for each hemisphere. A dipole was localized for each replication and the results were the lowest goodness-of-fit, or dipole fit error, was kept. The dipole parameters were noted for further analyses. The dipole coordinates were overlaid back onto the MRI to allow visualization of functional location relative to the lesion. Two-tailed t-tests (corrected for unequal variances) were used to compare the P100m dipole parameters between left versus right hemifield stimulations and affected versus unaffected cortical hemisphere.
RESULTS Dipole localizations for the P100m were attempted in all patients to both hemifield stimulations. In 11/12 patients, left hemifield stimulation localized to right occipital cortex, as expected. In 10/12 patients, right hemifield stimulation localized to left occipital cortex. Figure 1 shows an example of a clear P100m waveform (top) and a poorer quality, but localizable, P100m response (bottom). Figure 2 shows every location of each subject’s VEF dipoles overlaid on their own MRIs. P100m latencies were not significantly different between left hemifield (102.1 milliseconds 6 5.8 standard error of the mean [SEM]) and right hemifield (124.3 6 10.5) stimulations. Dipole fit errors also were not significantly different between left hemifield (17.1% 6 3.1 SEM) and right hemifield (23.8 6 5.4) stimulations, and dipole moments were not significantly different between left hemifield (24.0 A$m2 6 2.6 SEM) and right hemifield (25.2 6 2.6) stimulations.
Since there were no significant differences between left and right hemifield stimulations, data were regrouped into affected versus unaffected hemispheres and recompared. The dipole fit parameters for the P100m, including latency of peak, fit error, source strength (moment), and 3-dimensional coordinates, organized by affected versus unaffected hemispheres, are contained in Table 2. For the y-coordinate, negative values refer to right occipital cortex and positive to left occipital cortex. The mean and standard errors for the dependent variables submitted to statistical comparisons are contained in Table 3. Again, there were no significant differences between affected and unaffected hemisphere on measures of latency, error and moment; however, the absolute value of the y-coordinate was significantly different between the affected and unaffected hemispheres (P , 0.02). The dipoles in the affected hemisphere were displaced more laterally (2.0 units 6 0.18) compared with the dipoles in the unaffected hemisphere (1.2 units 6 0.25). X-coordinate (positive to negative: frontal to occipital) and z-coordinate (positive to negative: superior to inferior) parameters were not significantly different between the affected and unaffected hemispheres.
DISCUSSION The PRVEF was obtainable in our clinical pediatric population. As expected, left and right hemifield stimulations were equally likely to evoke a localizable P100m (92% vs. 83%, respectively) and did not demonstrate any differences in dipole latency, moment, error, or any of the other fit parameters. In contrast to the extant electrical VEP results (Blumhardt et al., 1982; Kuroiwa and Celesia, 1981), which demonstrated amplitude asymmetries between the P100 in the affected and unaffected hemispheres, the P100m in our study did not differentiate between affected and unaffected hemispheres on measures of latency, dipole moment strength or dipole fit error. However, our finding is not entirely unexpected as Holder (1985) reported that normal PRVEPs were associated with full and normal visual fields while abnormal or equivocal VEPs were associated with visual field defects, and our entire cohort, except one patient, had full and normal visual fields. Unfortunately, electrical VEPs were not performed in our study because this would have provided additional support for Holder’s (1985) assertion. Interestingly, there is a dichotomy between the goals of recording electrical versus magnetic visual evoked responses. Wenzel et al. (1988) reported abnormal PRVEP in children with
FIG. 1. Examples of the pattern-reversal visual evoked field with a clear P100m (top) and a poorer quality P100m (bottom). Tracings are averaged data from 100 trials with 151 sensors overlaid. VEF, visual evoked field; VEP, visual evoked potential. 458
Copyright Ó 2014 by the American Clinical Neurophysiology Society
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
VEF Displacement Due to Occipital Lobe Lesions
FIG. 2. Dipole fit locations for the pattern-reversal visual evoked field, for each patient, overlaid on coregistered axial MRI slices. Slices are presented in radiologic convention.
occipital lobe tumors when tested with small-sized checks. In our standard clinical MEG protocol (Sharma et al., 2007), large checks are used intentionally so as to obtain a VEF response that would meet the minimum signal-to-noise requirements for a robust dipole fit. Although it would be of interest in the future to test patients with both large and small checks, in the MEG, it is preferable to Copyright Ó 2014 by the American Clinical Neurophysiology Society
select a check size large enough to obtain an adequately clear PRVEF for dipole fitting. Because we were able to obtain dipole localizations in our cohort, our most noteworthy finding is a significant shift in the ycoordinate, whereby the dipole in the affected hemisphere demonstrated a significant lateral displacement relative to the dipole 459
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
E. W. Pang et al.
TABLE 2.
Dipole Fit Parameters for Each Patient Affected Side
Subject Number 1 2 3 4 5 6 7 8 9 10 11 12
Unaffected Side
Latency
Error
Moment
x
y
z
Latency
Error
Moment
x
y
z
d 105.6 112.0 d 96.0 150.4 161.6 81.6 121.6 142.4 86.4 84.4
d 18.13 39.35 d 8.0 7.87 15.29 20.07 26.49 38.42 20.99 20.38
d 13.69 26.09 d 22.57 39.22 35.93 21.21 21.66 25.72 23.01 8.45
d 26.8 27.4 d 28.6 25.5 25.9 26.4 25.5 24.7 26.4 28.3
d 2.8 1.9 d 2.1 2.1 1.4 1.3 22.1 22.8 21.5 22.4
d 6.1 3.4 d 2.7 4.9 5.4 4.7 7.0 3.5 6.0 4.2
102.4 107.2 118.4 96.0 97.6 d 78.4 88.0 139.2 137.6 176.0 83.2
10.56 21.65 18.07 3.39 11.11 d 3.37 14.0 61.41 27.42 32.26 7.75
36.48 13.64 20.47 24.13 21.69 d 32.93 36.27 17.24 30.93 18.13 27.48
26.8 28.1 26.6 27.4 28.4 d 26.4 25.8 25.6 26.1 24.1 27.2
20.9 21.4 21.9 21.0 20.4 d 21.0 21.3 3.2 1.3 1.0 0.3
3.8 4.8 4.5 4.3 3.4 d 4.5 4.9 4.2 3.9 7.8 5.5
location in the unaffected hemisphere. Most likely this reflects a mass effect of the lesion. This mass effect may provide an additional explanation for the presence of amplitude effects in the electrical VEP data (Blumhardt et al., 1982; Kuroiwa and Celesia, 1981) but not in our neuromagnetic data. The VEP is measured from three electrodes placed at standard fixed locations over occipital scalp. In the event that functional cortex is displaced, the electrodes are no longer situated over the functional cortex or the site of maximal response. This will be measured by the electrode as a diminished response. However, the MEG sensors acquire data over the entire occipital area, and the dipole is fit to the maximal response, even if it is displaced. It is important to point out the sparcity of development data regarding the PRVEF. While the electrical VEP has been well studied in children (Allison et al., 1984; Fenwick et al., 1981), and Armstrong et al. (1991) included an adolescent cohort in the magnetic PRVEF, to our knowledge, there has been no large-scale systematic study of the PRVEF in children using MEG. The results of this study cannot rule out the possibility that our findings are simply because of the developmental effects. As well, since our analyses were conducted within subject, and thus, a control group was not required, per se, there is a need to conduct future large-scale developmental studies in control children. Finally, a future comparison of the electrical VEP and magnetic VEF responses in the same subject, and in pediatric cohorts, would be helpful in disentangling the effects of developmental changes and neural plasticity. Our finding of a displacement in the PRVEF location in conjunction with intact visual fields suggests that function can be preserved when functional cortex is shifted but not when it is
TABLE 3.
damaged. Streletz et al. (1981) reported some form of VEF abnormality in their group of 20 patients with occipital lobe abnormalities; however, 18 of these patients had occipital infarcts. Presumably, an infarct resulted in damage to functional cortex and is therefore consistent with a VEP abnormality. In retrospect, our selection of patients with occipital lobe tumors created a very specific and homogenous patient cohort; in future, it would be of interest to examine the MEG PRVEF in other cohorts with different occipital lobe abnormalities. As well, it would be important to measure the size of the lesion and its medial/lateral extent within the occipital lobe to better understand if the PRVEP displacement is related to lesion size. However, the real value of MEG VEF results resides in its potential impact on our healthcare system by helping to triage and manage diagnostic imaging resources. For example, a young patient with visual complaints would be placed on a waiting list for a sedated MRI slot with no real indications of urgency. However, if this patient were offered an MEG and if asymmetric VEF locations were noted, this would emphasize the need to expedite the MRI, but if the VEFs were normal, then other clinical investigations should be pursued while waiting for the MRI. In summary, we have demonstrated mass effects on the dipole location of a visual evoked response in a group of children with occipital lobe tumors. This would suggest that the MEG VEF may be a diagnostic tool that is sensitive enough to identify the mass effects of a lesion on functional cortex and may be useful as a screening test before subjecting a young patient to (1) a long waiting list for an MRI and (2) an MRI done under general anesthesia. This demonstrates the added value of MEG recordings as a tool in the neurologic examination.
Comparison of P100m Dipole Parameters Between Affected and Unaffected Hemispheres
Affected side Mean 6 SEM Unaffected side Mean 6 SEM P (t-test)
n
Latency
Error
Moment
x-Coordinate
y-Coordinate (Absolute Value)
z-Coordinate
10
114.2 6 9.6
21.5 6 3.6
23.8 6 3.0
26.6 6 0.4
2.0 6 0.2
4.8 6 0.5
11
111.3 6 9.3 0.82
19.2 6 5.3 0.71
25.4 6 2.5 0.67
26.6 6 0.4 0.96
1.2 6 0.2 0.014*
4.7 6 0.4 0.85
*significant (p,0.05)
460
Copyright Ó 2014 by the American Clinical Neurophysiology Society
Journal of Clinical Neurophysiology Volume 31, Number 5, October 2014
ACKNOWLEDGMENTS The authors would like to thank Rohit Sharma, Amrita Viljoen, and Stephanie Holowka for assistance with data collection and Matt J. MacDonald for editorial assistance. REFERENCES Allison T, Wood CC, Goff WR. Brain stem auditory, pattern-reversal visual, and short-latency somatosensory evoked potentials: latencies in relation to age, sex, and brain and body size. Electroencephalogr Clin Neurophysiol 1983;55:619–636. Allison T, Hume AL, Wood CC, Goff WR. Developmental and aging changes in somatosensory, auditory and visual evoked potentials. Electroencephalogr Clin Neurophysiol 1984;58:14–24. American Encephalographic Society. Guideline nine: guidelines on evoked potentials. J Clin Neurophysiol 1994;11:40–73. Aminoff MJ, Goodin DS. Visual evoked potentials. J Clin Neurophysiol 1994;11:493–499. Armstrong RA, Slaven A, Harding GF. Visual evoked magnetic fields to flash and pattern in 100 normal subjects. Vision Res 1991;31:1859–1864. Barnikol UB, Amunts K, Dammers J, et al. Pattern reversal visual evoked responses of V1/V2 and V5/MT as revealed by MEG combined with probabilistic cytoarchitectonic maps. Neuroimage 2006;31:86–108. Blumhardt LD, Barrett G, Kriss A, Halliday AM. The pattern-evoked potential in lesions of the posterior visual pathways. Ann N Y Acad Sci 1982;388:264– 289. Burgess RC, Funke ME, Bowyer SM, et al. American clinical magnetoencephalography society clinical practice guideline 2: presurgical functional brain mapping using magnetic evoked fields. J Clin Neurophysiol 2011;28(4):355–361. Chen WT, Ko YC, Liao KK, et al. Optimcal check size and reversal rate to elicit pattern-reversal MEG responses. Can J Neurol Sci 2005;32:218–224. Chiappa KH, Hill RA. Pattern-shift visual evoked potentials: interpretation. In: Chiappa KH, ed. Evoked potentials in clinical medicine. 3rd ed. Philadelphia: Lippincott-Raven, 1997: chap. 3. Chuang NA, Otsubo H, Pang EW, Chuang SH. Pediatric magnetoencephalography and magnetic source imaging. Neuroimaging Clin N Am 2006;16:193–210. Cuffin BN, Cohen D. Comparison of magnetoencephogram and electroencephalogram. Electroencephalogr Clin Neurophysiol 1979;47:132–146. Fenwick PB, Brown D, Hennesy J. The visual evoked response to pattern reversal in “normal” 6–11 year old children. Electroencephalogr Clin Neurophysiol 1981;51:49–62.
Copyright Ó 2014 by the American Clinical Neurophysiology Society
VEF Displacement Due to Occipital Lobe Lesions
Hari R, Salmelin R. Magnetoencephalography: from SQUIDs to neuroscience. Neuroimage 2012;61:386–396. Hashimoto T, Kashii S, Kikuchi M, et al. Temporal profile of visual evoked responses to pattern-reversal stimulation analyzed with a whole-head magnetometer. Exp Brain Res 1999;125:375–382. Hatanaka K, Nakasato N, Seki K, et al. Striate cortical generators of the N75, P100 and N145 components localized by pattern reversal visual evoked magnetic fields. Tohoku J Exp Med 1997;182:9–14. Holder GE. Pattern visual evoked potential in patients with posteriorly situated space-occupying lesions. Doc Ophthalmol 1985;59:121–128. Kuroiwa Y, Celesia GG. Visual evoked potentials with hemifield pattern stimulation: their use in the diagnosis of retrochiasmatic lesions. Arch Neurol 1981;38:86–90. Matuz T, Govindan RB, Preissl H, et al. Habituation of visual evoked responses in neonates and fetuses: a MEG study. Dev Cogn Neurosci 2012;2:303–316. Nakamura A, Kakigi R, Hoshiyama M, et al. Visual evoked cortical magnetic fields to pattern reversal stimulation. Brain Res Cogn Brain Res 1997;6:9–22. Nakasato N, Yoshimoto T. Somatosensory, auditory, and visual evoked magnetic fields in patients with brain diseases. J Clin Neurophysiol 2000;17:201–211. Nakasato N, Seki K, Fujita S, et al. Clinical application of visual evoked fields using an MRI-linked whole head MEG system. Front Med Biol Eng 1996;7:275–283. Otsubo H, Snead OC. Magnetoencephalography and magnetic source imaging in children. J Child Neurol 2001;16:227–235. Perfetti B, Franciotti R, Della Penna S, et al. Low- and high-frequency evoked responses following pattern reversal stimuli: a MEG study supported by fMRI constraint. Neuroimage 2007;35:1152–1167. Seki K, Nakasato N, Fujita S, et al. Neuromagnetic evidence that the P100 component of the pattern reversal visual evoked response originates in the bottom of the calcarine fissure. Electroencephalogr Clin Neurophysiol 1996;100:436–442. Sharma R, Pang EW, Mohamed I, et al. Magnetoencephalography in children: routine clinical protocol for intractable epilepsy at the Hospital for Sick Children. In: Cheyne D, Ross B, Stroink G, Weinberg H, eds. New Frontiers in Biomagnetism. 2007:685–688. (Elsevier Canada, Toronto; Intl Congress Series, vol. 1300). Shigeto H, Tobimatsu S, Yamamoto T, et al. Visual evoked cortical magnetic responses to checkerboard pattern reversal stimulation: a study on the neural generators of N75, P100 and N145. J Neurol Sci 1998;156:186–194. Streletz LJ, Bae SH, Roeshman RM, et al. Visual evoked potentials in occipital lobe lesions. Arch Neurol 1981;38:80–85. Wenzel D, Brandl U, Beck JD, et al. Visual evoked potentials in tumors from orbita to occipital lobe in childhood. Neurosurg Rev 1988;11:279–286.
461
