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tutorthammy
IdentificationofAbnormalNeuromagneticSignaturesinthe.pdf
Research Submission
Identification of Abnormal Neuromagnetic Signatures in the Motor Cortex of Adolescent Migrainehead_1674 1005..1016
Xiaoshan Wang, MD, PhD; Jing Xiang, MD, PhD; Yingying Wang, MSc; Maria Pardos, MD; Lu Meng, MSc; Xiaolin Huo, PhD; Milena Korostenskaja, PhD; Scott W. Powers, PhD; Marielle A. Kabbouche, MD;
Andrew D. Hershey, MD, PhD
Objective.—To investigate the functional abnormalities of the motor cortices in children with migraine using magnetoen- cephalography (MEG) and a finger-tapping task.
Background.—Cortical hyperexcitability has been reported in adults with migraine using MEG. Many children with migraine report difficulty with motor functioning. There is no report on motor-evoked magnetic activation in children with migraine using MEG and the latest signal processing methods.
Methods.—Ten children with migraine (all female, 9 right-handed and 1 left-handed, aged 13-17 years) and 10 age- and gender-matched healthy children were studied with a 275-channel MEG system. After hearing a unilateral, randomly presented sound cue (500 Hz, 30 milliseconds square tone), each subject immediately performed a brisk index finger tapping with either the right or the left index finger. The auditory stimuli consisted of 200 trials of square tone, 100 trials per ear, randomly distributed. The latency and amplitude of neuromagnetic responses were analyzed with averaged waveforms. Neuromagnetic sources were estimated using synthetic aperture magnetometry (SAM). SAM images were normalized for each participant for group comparison.
Results.—In comparison with healthy children, children with migraine had prolonged latency of motor-evoked magnetic response in the right hemispheres during left finger movement (62.33 � 34.55 milliseconds vs 34.9 � 17.29 milliseconds, P < .05). In addition, children with migraine had stronger activation in the motor cortex during right finger movement (8097.46 � 5168.99 vs 4697.54 � 3194.74, P < .05).
Conclusions.—The results suggest that there are neurophysiological changes in the motor cortices of children with migraine that can be measured with neuromagnetic imaging techniques. The findings expand the ability to study the cerebral mechanisms of migraine using MEG and may facilitate the development of new therapeutic strategies in migraine treatment via alterations in cortical excitability.
Key words: migraine, magnetoencephalography (MEG), synthetic aperture magnetometry (SAM), children, pediatric
(Headache 2010;50:1005-1016)
From the MEG Center, Department of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA (X. Wang, J. Xiang, Y. Wang, M. Pardos, L. Meng, X. Huo, M. Korostenskaja, M.A. Kabbouche, and A.D. Hershey); Department of Neurology, Nanjing Brain Hospital, Nanjing Medical University, Jiangsu, China (X. Wang); University of Cincinnati, College of Medicine, Cincinnati, OH, USA (J. Xiang, S.W. Powers, M.A. Kabbouche, and A.D. Hershey); Department of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA (S.W. Powers).
Address all correspondence to A.D. Hershey, Cincinnati Children’s Hospital Medical Center, Department of Neurology, 3333 Burnet Avenue – MLC 2015, Cincinnati, OH 45229-3039, USA.
Accepted for publication March 22, 2010.
Conflicts of Interest: None
ISSN 0017-8748 doi: 10.1111/j.1526-4610.2010.01674.x Published by Wiley Periodicals, Inc.
Headache © 2010 American Headache Society
1005
Migraine is characterized by episodes of moder- ate to severe pain that is a pulsating headache with a focal location and can be associated with nausea, vomiting, photophobia, and phonophobia.1 Addi- tional neurological dysfunction can be seen during an acute attack including auras, difficulty thinking and functioning and cutaneous allodynia. Migraine fre- quently begins in childhood increasing in adolescence and early adult life.2-5 Until puberty, the prevalence of migraine is the same in boys and girls. After puberty, the ratio of females to males is approximately 3 : 1. Pediatric migraine is increasingly being recognized as a significant health problem,1,4,6 but the underlying neuropathophysiology of pediatric migraine is still not well understood.
Migraine was originally speculated to be a disease solely of the cranial vascular structures.1,4,6
Clinical and neuroimaging studies demonstrated the involvement of the cerebral cortex with this brain region serving a primary role in the cascade of migraine attacks.1,4,6,7 Abnormal cortical excitability, thought to be due to calcium channelopathy, appears to play an important role in predisposing to sponta- neous, cortical spreading depression suggested as one basis for the pathophysiology of migraine with aura.8
Functional magnetic resonance imaging (fMRI) has demonstrated abnormal activation in the contralat- eral visual cortex in migraine with aura. Transcranial magnetic stimulation (TMS) studies have shown gen- eralized interictal change of excitability in the cere- bral cortex in migraine with alteration of excitability in the motor and visual cortices.9
Magnetoencephalography (MEG) is a relatively new and non-invasive tool for investigating functional activation in the brain.10 MEG measures very weak magnetic fields associated with electric neural firing in the human brain11 with a time resolution under 1 millisecond and spatial discrimination of 2-3 mm for sources in the cerebral cortex.10,12 MEG is considered to be superior to scalp electroencephalography (EEG) because electric signals can be distorted by skull, skin, and other tissues while magnetic signals can pass through these tissues without significant distor- tion.10,12 Previous MEG reports13,14 have shown that neuromagnetic changes during migraine consist of 3 features: suppression of spontaneous cortical activity,
long duration field changes, and large amplitude waves (LAW).The suppression of spontaneous cortical activ- ity and long duration field changes seem consistent with spreading cortical depression (SCD) findings in experimental animal models as measured by both electrocorticography (ECoG) and MEG.15 The LAW is a brief spike like event and is not a reference to the large amplitude direct current (DC) waves that are seen in SCD. It remains a curious phenomenon.
Magnetoencephalography tests have become as one part of standardized clinical workup for preop- erative evaluation for epilepsy surgery.20,21 The use of MEG in pediatric epilepsy is growing because it pro- vides unique information for patients who do not have satisfactory indication of epilepsy localization from seizure semiology, EEG, and magnetic reso- nance imaging (MRI).12,20,21 Synthetic aperture mag- netometry (SAM) is a widely used nonlinear beamformer method18,19 that can detect the activation and depression of brain activity.18,19 To image the acti- vation and depression of brain activity, SAM creates statistical parametric images showing a spatial distri- bution of spectral power change by computing the differences of spectral power between active and control time windows. Activation is also called syn- chronization, which indicates that the spectral power in the active time window is statistically higher than that in the control time window. Depression is also called desynchronization, which indicates that the spectral power in the active time window is statisti- cally lower than that in the control time window. Since SAM produces statistical images, the measure- ments of voxels have no unit. A SAM beamformer algorithm has been successfully used to detect activa- tion and depression in the mu and beta frequency bands in the sensorimotor cortex in normal subjects22
as well as in the alpha and gamma frequency bands in the visual cortex in a patient with migraine.17
However, SAM has not been used in the study of neural excitability in the motor cortex in pediatric migraine.
The objective of this study was to obtain some pilot data to look at the role of MEG in pediatric migraine with a specific focus on the motor system. The involvement of the motor system with migraine is often associated with patients experiencing hemiple-
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gic migraine.23 Diagnostic criteria for migraine include aggravation of the headache pain by motor activity such as walking and climbing stairs.24 We hypothesized that the functionality of the motor cortex would be significantly altered in children with true episodic migraine. We quantified the differences of neuromagnetic brain activation between acute migraine and healthy controls without a headache using both the conventional waveform analyses and SAM analyses. Since the ratio of female to male of our clinical migraine patients is approximately 3.8:1.0,1,4,25 to minimize gender effects, this study focused on the neuromagnetic abnormalities in girls with migraine. SAM was used in this study because our recent data suggest that the motor cortex gener- ates high-gamma neuromagnetic signals26 and SAM can localize these high-gamma signals. Since there are neuromagnetic developmental changes in the motor system in healthy children, to study the neuromag- netic abnormalities in children with migraine, it seems important to determine if there are any neuromag- netic abnormalities in children with migraine as compared with age- and gender-matched healthy chil- dren. The results of the present study may lay a foun- dation for us to address other research questions such as the differences of ictal and interictal neuromag- netic activation in migraine.
MATERIALS AND METHODS Subjects.—Ten subjects with acute migraine
(female; mean age 15.3 � 1.49, range 13-17 years), meeting International Classification of Headache Disorders, 2nd Edition (ICHD-II)24 with an acute headache were evaluated and compared with 10 controls (female, mean age 14.4 � 1.43; range 12-17 years) (see the Table). Parents or guardians of patients/controls gave written informed consent to participate in the study, which was approved by the Cincinnati Children’s Institutional Review Board.
Subjects with acute migraine underwent standard evaluation for an acute migraine or a chronic migraine with an acute exacerbation with no change in the clinical management. Subjects who had failed at home treatment and were referred for acute out- patient or inpatient treatment were identified. The MEG studies were performed prior to initiation of
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treatment. All subjects had normal hearing and hand movement. Subjects who had an implant (ie, braces) that can produce visible magnetic noise in the MEG data or demonstrated or expressed noticeable anxiety and/or could not readily communicate with personnel operating the MEG equipment were excluded from the study.
Tasks.—All subjects and controls performed a brisk index finger tapping with either the right or the left index finger immediately after hearing an acous- tic cue (500 Hz, 30 milliseconds square tone). Subjects were instructed to press a response button with the index finger that was ipsilateral to the tone presented. A trigger was sent to the MEG system from the response box when the button was pressed. Other body parts were kept still with the eyes fixed to a target during the paradigm. The stimuli consisted of 200 trials of square tones, 100 trials per ear, and were presented randomly through a plastic tube and ear- phones. The stimulation presentation and response recording were accomplished with BrainX software,18
which is a software package based on DirectX (Microsoft Corporation, Redmond, WA, USA). The entire procedure took about 15 minutes.
Data Acquisition.—The MEG signals were recorded in a magnetically shielded room using a whole head CTF 275-Channel MEG system (VSM MedTech Systems Inc., Coquitlam, BC, Canada) in the MEG Center at Cincinnati Children’s Hospital Medical Center. Before data acquisition, an electro- magnetic coil was attached to the nasion and left and right pre-auricular points of each subject. These 3 coils were subsequently activated at different fre- quencies for measuring subjects’ head positions relative to the MEG sensors. Each subject lay com- fortably supine during the entire procedure with their arms resting on either side. The sampling rate of the MEG recordings was 6000 Hz per channel (very high-frequency signals were analyzed for another study). An acquisition window was set to 3000 milliseconds per trial, with 2000 milliseconds pre-trigger (or pre-finger typing). The trigger was sent to the MEG system from a response when a button was pressed. Data were recorded with a noise cancellation of third-order gradients without on-line filtering.
Pediatric Brain Templates developed by the Cin- cinnati Children’s Imaging Research Center were used for source localization and visualization.27,28
Data Analysis.—The MEG data were manually averaged after the removal of eye movements and other artifacts. Movement-evoked fields (MEFs) were investigated via DataEditor (CTF Systems Inc.). MEG data were averaged for identification of evoked magnetic responses. The averaged MEG data were preprocessed by removing DC offset based on pre- trigger. The off-line low pass filter (30 Hz) and high pass filter (1 Hz) were applied to the manually aver- aged MEG data. The latencies and the peak ampli- tudes of the averaged MEG waveform were measured for each recognizable component with DataEditor.
Neuromagnetic activation and suppression were analyzed using SAM.18,19 SAM images were com- puted with raw MEG data without averaging or filtering. We normalized SAM images for each partici- pant for group comparison. Two analysis windows were defined to quantitatively estimate the neuro- magnetic activation: one active and one control. The time window covering the first peaks of the MEF was analyzed with SAM as an active state. The control state was chosen 600 milliseconds pre-trigger.
Building on our previous experiments,18,19 high- gamma activation (in 65-150 Hz) with focal increases of spectral power around the motor cortex was ana- lyzed using SAM. A 3D head model was created with MR templates. SAM images were normalized since the SAM T-value varied among participants, so the voxel values (or “T value”) of SAM images from all participants were in the range of -100 to 100 (there was no unit). To delineate the region of brain activa- tion, the T value threshold were determined by co-registering SAM data to MEG data program using 3 complementary fiducial markers with the Magnetic Source Locator19 followed by adjusting the SAM T value until SAM activation or suppression only appeared on the brain tissue. The activation threshold T-value was 80; the suppression threshold T-value was -80. This means that, a T value above 80 was “activa- tion”; a T value below -80 was “suppression.” Both activation and suppression were considered func- tional brain activities; the T-value between -80 to 80
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was “background activation” or noise. The volumes of a SAM image above 80 or below -80 were considered to represent the volume of functional activation. Intensity volume was also used as a quantitative parameter of eloquent regions with the product of T-value and volume above 80 or below -80.29,30 Since the size of the subject’s head and the distance between head and MEG sensor might affect the amplitude of neuromagnetic responses, we measured the cortical source amplitudes of virtual sensors at the motor cortex.29
Statistical Analysis.—A paired t-test analysis was applied to the latencies and amplitudes of the first post-movement peaks of MEF between migraine sub- jects and controls. The SAM values of voxels display- ing the strongest signal power changes in the sensorimotor cortex were statistically compared with a 2-sample Student’s t-test for migraine subjects and
controls. The threshold of statistical significance for differences was set at P < .05.
RESULTS Morphology.—The MEG waveforms from
migraine subjects and controls showed at least one response (deflection) in the hemisphere contralateral to the finger moved with a small neuromagnetic deflection in the hemisphere ipsilateral to the finger moved. Typical responses in the contralateral and ipsilateral hemispheres following finger tapping are shown in Figures 1 and 2. The first response was the most robust in both migraine subjects and controls with the MEG waveforms from migraine subjects having a larger variation in morphology.
Latency.—The latency of the first response identi- fied in the ipsilateral and contralateral hemispheres of migraine patients were significantly slower (49.94 � 34.06 milliseconds and 62.33 � 34.55 milli- seconds) compared with controls (21.21 � 8.05
Fig 1.—Magnetoencephalography (MEG) waveforms showing neuromagnetic activation evoked by left finger tapping in a migraine patient (“Migraine”) and a healthy participant (“Normal”). There are clear differences in the morphology of the MEG waveforms. The latency of the first response in migraine is longer than that in normal. The “Trigger” indicates the start of finger tapping. The “MEF” indicates the first response of movement-evoked magnetic fields.
Fig 2.—Magnetoencephalography (MEG) waveforms showing neuromagnetic activation evoked by right finger tapping in a migraine patient (“Migraine”) and a healthy subject (“Normal”). There are noticeable differences in the morphol- ogy of the MEG waveforms. The amplitude of the first response in migraine is larger than that in normal. The latency of the first response in migraine is longer than that in normal. The “Trigger” indicates the start of finger tapping. The “MEF” indicates the first response of movement-evoked magnetic fields.
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milliseconds and 34.9 � 17.29 milliseconds, P < .05). Migraine subjects also had prolonged latency of motor-evoked magnetic response in ipsilateral and contralateral hemispheres (Fig. 3).
Amplitude.—The amplitude of the neuromagnetic responses in the MEG waveforms recorded from migraine patients and normal subjects was measured and analyzed. The amplitude of the first response in migraine subjects and controls was quantified and there was no statistical difference (P > .05). We mea- sured the cortical source amplitudes and found that patients with migraine had significant stronger source activation during right finger tapping than the normal children did (64.0 nA-m vs 47.8 nA-m; P < .05). The results of source activation are shown in Figure 4.
Magnetic Source Location.—The main activation of neuromagnetic responses during finger movement was localized in the contralateral primary motor cortex in all migraine subjects (100%, 10/10) and con- trols (100%, 10/10). Strong and widely distributed activation in the supplementary motor area during finger movement was mainly found in migraine sub- jects (100%, 10/10 vs 10%, 1/10). Figure 5 shows the centers and connections of the activation in 3D. Figure 6 shows the centers of the activation in the motor cortices in 2D.
Activation Volume.—To quantify the activation in the motor cortices, the total values of SAM images in migraine subjects and in controls were compared. There was no difference between migraine subjects and controls in terms of SAM activation volumes in the primary motor cortex during finger movement. However, there was a significant difference of the total value of activation in SAM images in the supple- mentary motor cortex during right finger movement between controls and migraine subjects (8097.46 � 5168.99 vs 4697.54 � 3194.74, P < .05). Since SAM images were produced by statistically comparing neu- romagnetic spectral power over active and control time windows, there was no units for SAM value.31
DISCUSSION Magnetoencephalography is a relatively new
clinical technology for measuring neuromagnetic signals associated with electric neural activities in the brain.18,19,29,30 The development of MEG methods has made it possible to estimate functional brain activa- tion with spatial, temporal, spectral, frequency as well as volumetric descriptions.29,30 SAM, one of the newly developed MEG methods, allows for noninvasively and statistically imaging functional brain activa- tion18,19,29,30 and revealing functional abnormalities in
Fig 3.—The graph showing the latency of the first movement-evoked neuromagnetic response in migraine patients and normal children. LFM-RHR: left finger movement-right hemisphere response; LFM-LHR: left finger movement-left hemisphere response; RFM-RHR: right finger movement-right hemisphere response; RFM-LHR: right finger movement-left hemisphere response.
P < .05.
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the developing brain.18,19,29,30 By comparing spectral power over active and control time windows, SAM can quantitatively determine if a brain area has hyper- or hypo-excitability.17,22,29 To investigate the activation of motor cortex in children with episodic migraine, the present study investigated movement- evoked magnetic fields (MEFs) with a finger-tapping task. The finger-tapping task is a widely used proce- dure for evaluating motor function and has been reported to be slower in the migraine subjects com- pared with controls.32 The functionality of the motor cortex in migraine can quantitatively evaluated using MEG with the repetitive finger-tapping task as a measure of motor performance. Though MEG has been used in the study of migraine in adults with spontaneous and visual evoked magnetic fields in low-frequency ranges,13,14,17,33 the neuromagnetic abnormality in a wide frequency range (1-300 Hz) in the motor cortex in children with migraine has not been reported. Therefore, we analyzed the MEG data recorded from children with episodic migraine with both the conventional methods as well as newly developed MEG methods.
A significant difference between migraine patients and controls in terms of the latency of the first response in MEFs has been found by analyzing MEG data with the conventional averaged wave- forms (Fig. 1). Migraine patients had prolonged
Fig 4.—The graph showing the amplitude of movement-evoked cortical source activation in migraine patients and normal children. LFM-RHR: left finger movement-right hemisphere response; LFM-LHR: left finger movement-left hemisphere response; RFM- RHR: right finger movement-right hemisphere response; RFM-LHR: right finger movement-left hemisphere response. *P < .05.
Fig 5.—Volumetric magnetoencephalography results com- bined with 3D MR images (magnetic source imaging, MSI) showing the SAM imaging of movement-elicited source activa- tion in 65-125 Hz. The red and yellow areas indicate regions of neuromagnetic activation (or synchronized neural firing). The neuromagnetic activation elicited by right finger movement is localized in the contralateral motor cortex in the healthy control. The neuromagnetic activation elicited by right finger movement is localized in the contralateral motor cortex as well as in the supplementary motor area in migraine. The threshold is set to 63 (<80) to show the center as well as the connection of the brain activation. The color bar indicates the color-coding of strength of activation.
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latency of motor-evoked magnetic response in ipsilat- eral and contralateral hemispheres during left finger movement. The latency delay may actually reflect true cortical delay and/or delay in response to auditory cues because the patient was in pain and not reacting quickly enough. According to the waveforms, it is more than likely that the cortical response was delayed because the distance between the pre-trigger activation (readiness magnetic fields) and the MEF was clearly prolonged (see Fig. 2). Though the cere- bral mechanisms of the latency changes remain unclear, it is widely recognized that neurologic symp- toms are a prominent and often disturbing compo- nent of the migraine syndrome in many patients.34-36
Migraine-related neurologic symptoms include visual, sensory, language, and motor disturbance,
occurring in about one-quarter of migraine patients. These are classically transient, and are thought to occur as the result of cortical phenomena.34-36 Motor symptoms of aura have been classified as an atypical aura as hemiplegic migraine.34-36 The latency change observed in this study suggests that there is motor dysfunction in children with migraine.
A significant increase of source activation has been found in children with migraine as compared with controls using newly developed virtual sensor technology.29 We noted that the amplitude of the first response in MEFs did not shown significant abnor- malities in children with migraine. The reason is prob- ably that the conventional method analyzes MEG data at the sensor level. The amplitude of MEG signals at sensor levels might be affected by the size of
Fig 6.—Magnetoencephalography results combined with 2D MR images (magnetic source imaging, MSI) showing the center of SAM imaging of movement-elicited source activation in 65-125 Hz. The red and yellow areas indicate regions of neuromagnetic activation (or synchronized neural firing). The neuromagnetic activation elicited by right finger movement is localized in the contralateral motor cortex in the healthy control. The neuromagnetic activation elicited by right finger movement is localized in the contralateral motor cortex as well as in the supplementary motor area in migraine. The threshold is set to 80 to show the center of the brain activation. The color bar indicates the color-coding of strength of activation.
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the head and position of the head relative to the MEG sensors because the magnetic signals decay rapidly with distance.29,30 The increase of source acti- vation in the motor cortex in migraine is supported by several previous studies of visual and somatosensory evoked magnetic fields in migraine. One report14 has shown that a visual stimulation can elicit excessive neuromagnetic activation in migraine patients. In the somatosensory system, MEG has identified a popula- tion of neurons in the primary somatosensory cortex underlying the N20m with hyperexcitability linked to the frequency of migraine attacks.37 This hyperex- citability appears not to be related to habituation since habituation was not found in the control sub- jects.37 In contrast, the magnitude of P35m is not pathophysiologically linked to the interictal state of migraine.37 Furthermore, the cellular mechanisms causing interstimulus interval-dependent depression of N20m and P35m are not altered in migraine.37
Taken together, our data and previous reports suggest that migraine is probably associated with cortical hyperexcitability.
One of the most interesting findings in source analyses is that children with migraine have stronger activation in the supplementary motor area during the finger movement. There was a significant differ- ence of the total value of activation in SAM images during right finger movement between controls and migraine subjects. According to our data, neural mag- netic activation in the contralateral primary motor area is consistently localizable in all controls and migraine subjects. There was no statistical difference between migraine subjects and controls in terms of activation in the primary motor area. However, acti- vation in supplementary motor area was mainly iden- tified in children with migraine but not normal children. This implicates the supplementary motor area as playing an important role in migraine attacks. This observation is concordant with several previous reports.38,39 The supplementary motor area may be important in pain perception40 and may explain the strong activation in the supplementary motor area during the finger movement in migraine children. EEG studies have demonstrated elevated negativity over the supplementary motor area in children with migraine,38 while fMRI studies have suggested that
there is a shift of the center of supplementary motor area activation in migraine.39
High-frequency neuromagnetic signals in supple- mentary motor area in migraine have not been well understood. The results of the present study indicate that neuromagnetic signals up to 150 Hz can be iden- tified in supplementary motor area in migraine. Although low-frequency brain signals have been widely studied,10,11,13,14,41 high-frequency brain signals have rarely been examined. From our point of view, the conventional waveform mainly reveals low-frequency brain signals (~30 Hz). High-frequency brain signals can only be reliably detected by newly developed methods.29,42 In this study, changes in high-gamma oscillations in the motor cortex were evaluated with newly developed SAM.22 The SAM can detect high- frequency brain signals because it statistically deter- mines spectral power in certain frequency ranges between an active and control time windows.The accu- racy and reliability of SAM have been tested with somatosensory and visual evoked magnetic fields.17,22,29
To our knowledge, this is the first study of high- frequency neuromagnetic signals (~150 Hz) in the motor cortex in children with migraine. Gamma oscil- lations (~80 Hz) have been studied in humans with EcoG.43 It was observed gamma activity occurred over the central regions during movement and its topogra- phy was consistent with traditional maps of sensorimo- tor functional anatomy.43 Pain-induced gamma oscillations in primary somatosensory cortex are related to a complex cerebral network subserving con- scious perception of sensory events.44 The results of the present indicate that high-gamma activity (~150 Hz) occurs in the supplementary motor area in pediatric migraine. Our results are concordant with several pre- vious reports that the motor cortex activity was altered in pediatric migraine.9,23,35,45,46 Migraine subjects seem to have more excitable cortices than controls with this excitability potentially leading to the cascade of depo- larizing neurons, described as SCD.9,23,35,45,46
Both the conventional MEG waveforms and the newly developed SAM images revealed that the neu- romagnetic signals in motor system in children with migraine are altered as compared with normal con- trols. These results are clinically important for several reasons. First, neuromagnetic signals measured by
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MEG can be used as potential biomarkers for evalu- ating therapeutic effects.33 DC-MEG waveforms arising during migraine aura were studied and used to determine the effectiveness of prophylactic medica- tion therapy on neuronal hyperexcitability.33 We believe that newly developed MEG methods will facilitate the development of new treatment for migraine. Second, high-frequency neuromagnetic signals provide new opportunities to localize cortical hyperexcitability. Repetitive transcranial magnetic stimulation (rTMS)47 has shown intriguing results in migraine treatment and previous by normalizing cor- tical excitability.48,49 Since the effectiveness of rTMS in migraine treatment is dependent upon correct placement and aim of the rTMS device,48,49 localiza- tion of cortical hyperexcitability with MEG may provide important information to guide rTMS treat- ment (MEG-guided TMS) and the outcomes may be significantly improved.49-52 In addition, newly devel- oped MEG methods such as SAM can provide volu- metric, spectral, and frequency information about cortical dysfunction in migraine. Those additional information may facilitate the development of new therapeutic strategies in migraine treatment via alterations in cortical excitability with TMS or medications.33,49-52 Given that high-frequency neuro- magnetic signals are a new discovery, pathologic high- frequency neuromagnetic signals should provide novel insights into the pathophysiology of migraine. Improved treatment and prophylaxis solutions based on better understanding of mechanisms of migraine may efficiently protect children with migraine from progressing into a chronic condition with significant disability in the future.
Since this study was based on our normative MEG data from children and the patients were recruited through our routine headache clinics, the number of patients is very limited. For example, our patients might be approaching status migrainous. Consequently, the results based on this subpopulation of children with migraine may not well reflect the neuromagnetic abnormalities in pediatric migraine in general. In addition, it is necessary to study migraine with a large number of patients during and between migraine attacks. Furthermore, the correlation between the duration of migraine attack and the neu-
romagnetic activation remains unclear. However, based on the results of the present study, it is rational and feasible to anticipate that the aforementioned questions can be addressed with MEG technology noninvasive in the near future.
CONCLUSION The current study demonstrates that there are
measurable neuromagnetic abnormalities in children with migraine during finger tapping. Though it remains unclear why the latency of movement related neuromagnetic responses was significantly delayed and the excitability of motor cortex in the pediatric migraine was altered, this study provides pilot data for further investigation of the cerebral mechanisms of migraine with MEG and advanced signal process- ing methods. The findings may facilitate the develop- ment of new therapeutic strategies in migraine treatment via alterations in cortical excitability with TMS and other medications in the future.
Acknowledgment: This study was partially sup-
posed by a Trustee Grant to Dr. Jing Xiang from Cincin-
nati Children’s Hospital Medical Center, Cincinnati,
OH, USA.
STATEMENT OF AUTHORSHIP
Category 1 (a) Conception and Design
Andrew D. Hershey, Xiaolin Huo, Jing Xiang, Xiaoshan Wang, Scott W. Powers, Marielle A. Kabbouche
(b) Acquisition of Data Yingying Wang, Maria Pardos, Lu Meng, Jing Xiang, Milena Korostenskaja, Xiaoshan Wang
(c) Analysis and Interpretation of Data Xiaoshan Wang, Jing Xiang, Xiaolin Huo, Yingy- ing Wang, Andrew D. Hershey
Category 2 (a) Drafting the Article
Xiaoshan Wang, Jing Xiang, Andrew D. Hershey (b) Revising It for Intellectual Content
Scott W. Powers, Marielle A. Kabbouche, Xiaolin Huo, Xiaoshan Wang, Jing Xiang, Yingying Wang, Maria Pardos, Lu Meng, Milena Korostenskaja, Andrew D. Hershey
1014 June 2010
Category 3 (a) Final Approval of the Completed Article
Xiaoshan Wang, Jing Xiang, Yingying Wang, Maria Pardos, Lu Meng, Xiaolin Huo, Milena Korostenskaja, Scott W. Powers, Marielle A. Kab- bouche, Andrew D. Hershey
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