Periodic Discharges: Insight From Magnetoencephalography.

PURPOSE: This study used magnetoencephalography (MEG) dipole localization and coherence measurement to evaluate the magnetic fields associated with periodic discharges. The primary goal of the study was to evaluate whether MEG could consistently localize quasiperiodic discharges that were observed on the EEG portion of the recording. The secondary objective was to evaluate whether coherence measurements would correlate with topographic maxima of epileptiform activity. METHODS: A total of 13 inpatients, whose electrographic records demonstrated lateralized periodic discharges (LPDs), were recruited from Henry Ford Hospital neurology and intensive care units. Nine patients were found clinically to be in status epilepticus before the EEG determination of LPDs. Spontaneous cortical brain activity was recorded with 148-channel MEG for 10 minutes. Data were sampled at 508 Hz and DC-100 Hz and filtered from 1 Hz to 40 Hz. Interictal events were imaged with single equivalent current dipole localization. Magnetoencephalography coherence source imaging analysis was performed and compared with the cortical topography of LPD patterns and with the focal lesions seen on the MRI (9 patients) or computed tomography (5 patients) imaging modalities. RESULTS: The morphology of periodic waveforms was similar between EEG and MEG portions of the study. In patients with substrate positivity on imaging studies, coherence analysis revealed a tendency for LPDs to arise from the interface between the lesion and the surrounding, uncompromised cortex rather than from the lesion itself. In nonlesional patients with recent status epilepticus, the localization of maximal coherence was in the temporal lobes. CONCLUSIONS: This study demonstrated that MEG is able to detect and localize LPDs arising from damaged and adjacent cortex. The MEG coherence source imaging measurements also suggest the presence of epileptogenic networks perilesionally in cases with focal lesions on imaging. In patients without acute anatomic abnormality, the MEG coherence identified the epileptogenic networks in temporal lobe structures. Magnetoencephalography coherence source imaging may provide physicians with markers for differentiating between LPDs arising from acute injury currents versus LPDs arising from prolonged status epilepticus.

Slow brain activity (ISA/DC) detected by MEG.

Infraslow activity (ISA), direct coupled (DC), and direct current (DC) are the terms used to describe brain activity that occurs in frequencies below 0.1 Hz. Infraslow activity amplitude increase is also associated with epilepsy, traumatic brain injuries, strokes, tumors, and migraines and has been studied since the early 90s at the Henry Ford Hospital MEG Laboratory. We have used a DC-based magnetoencephalography (MEG) system to validate and characterize the ISA from animal models of cortical spreading depression thought to be the underlying mechanism of migraine and other cortical spreading depression-like events seen during ischemia, anoxia, and epilepsy. Magnetoencephalography characterizes these slow shifts easier than electroencephalography because there is no attenuation of these signals by the skull. In the current study, we report on ISA MEG signals of 12 patients with epilepsy in the preictal and postictal states. In the minutes just before the onset of a seizure, large-amplitude ISA MEG waveforms were detected, signaling the onset of the seizure. It is suggested that MEG assessment of ISA, in addition to activity in the conventional frequency band, can at times be useful in the lateralization of epileptic seizures.

An assessment of MEG coherence imaging in the study of temporal lobe epilepsy.

PURPOSE: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug-resistant temporal lobe epilepsy (TLE). METHODS: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject's magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome. KEY FINDINGS: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run-to-run (correlation > 0.90) using three 10-min epochs. SIGNIFICANCE: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run-to-run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decision-making where the laterality of TLE is questioned.

Shift work sleep disorder is associated with an attenuated brain response of sensory memory and an increased brain response to novelty: an ERP study.

STUDY OBJECTIVE: To study the neurophysiological changes in attention and memory functions in shift work sleep disorder (SWSD), using event-related brain potentials (ERPs). PARTICIPANTS: 9 healthy night workers (NW) (mean age = 40 y; SD +/- 8.9 y); 8 night workers meeting diagnostic criteria for SWSD (mean age = 37 y +/- 9.4 y) and 9 healthy day workers (DW) (mean age = 35 y +/- 7.3 y). METHODS AND PROCEDURE: Using standard PSG the sleep related measures (TIB, TST, SOL, SE, and sleep stage distribution) were obtained prior to EEG/ERP study. Measures of habitual sleep were obtained from 2 week sleep logs and sleepiness was assessed with standardized measures. Using 32-EEG leads the ERPs to 3 types of sounds (novel, duration deviant, and simple tone) were obtained. The mismatch negativity (MMN) reflecting memory processing and P3a-reflecting the shift of involuntary attention were obtained. STATISTICAL ANALYSIS: The statistical comparisons of ERPs and sleep related parameters were performed using repeated measured ANOVAs and t-tests where appropriate. RESULTS: Patients with SWSD had reduced TST and increased WASO relative to healthy workers. ERP results demonstrated significant attenuation of MMN amplitude over frontal regions in SWSD patients relative to NW and DW. In the SWSD patients, the P3a was increased to novelty across frontocentral brain regions with respect to the same locations in healthy controls. CONCLUSION: The ERP evidence of sensory memory reduction and attentional hyper-reaction to novel sound in conjunction with disturbed sleep suggests the need for more neurophysiological studies in SWSD workers.

Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study.

The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 +/- 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence.

Conversation effects on neural mechanisms underlying reaction time to visual events while viewing a driving scene using MEG.

Magnetoencephalography (MEG) imaging examined the neural mechanisms that modulate reaction times to visual events while viewing a driving video, with and without a conversation. Twenty-four subjects ages 18-65 were monitored by whole-head MEG. The primary tasks were to monitor a driving video and to depress a foot pedal in response to a small red light presented to the left or below the driving scene at unpredictable times. The behavioral reaction time (RT) to the lights was recorded. The secondary task was a hands-free conversation. The subject pressed a button to answer a ring tone, and then covertly answered pre-recorded non-emotional questions such as "What is your birth date?" RTs for the conversation task (1043 ms, SE=65 ms) were slightly longer than for the primary task (baseline no conversation (944 ms, SE=48 ms)). During the primary task RTs were inversely related to the amount of brain activity detected by MEG in the right superior parietal lobe (Brodmann's Area 7). Brain activity was seen in the 200 to 300 ms range after the onset of the red light and in the visual cortex (BA 19) about 85 ms after the red light. Conversation reduced the strengths of these regression relationships and increased mean RT. Conversation may contribute to increased reaction times by (1) damping brain activation in specific regions during specific time windows, or (2) reducing facilitation from attention inputs into those areas or (3) increasing temporal variability of the neural response to visual events. These laboratory findings should not be interpreted as indicative of real-world driving, without on-road validation, and comparison to other in-vehicle tasks.

Evidence for a frontal cortex role in both auditory and somatosensory habituation: a MEG study.

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.

Direct electrical stimulation of Heschl's gyrus for tinnitus treatment.

OBJECTIVES/HYPOTHESIS: The purpose of the study was to determine the effect of electrical stimulation of the auditory cortex in patients with tinnitus. STUDY DESIGN: Nonrandomized clinical trial. METHODS: Two patients with debilitating tinnitus refractory to conventional therapies were treated. Patients were evaluated with validated questionnaires and psychoacoustic measures to determine the frequency and pitch of their tinnitus. Tones at these frequencies were then presented to the first patient (RP) under magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to determine the tonotopic map for these frequencies in Heschl's gyrus. These tonotopic sites were targeted for implant with a quadripolar electrode. In the second patient (MV), only the fMRI tonotopic map was performed. These fMRI results detected an area of increased activity, which was selected as the site for the implanted bipolar electrode. RESULTS: Patient RP (bilateral tinnitus for 2 years) has experienced a sustained reduction to near elimination of tinnitus with intracerebral implanted electrodes, whereas patient MV (unilateral tinnitus for 7 years) had an unsustained reduction in her tinnitus. CONCLUSION: These findings suggest that the perception and annoyance of tinnitus may be modulated or reduced through electrical stimulation of the auditory cortex. These unsustained effects for patient MV may have been influenced by the longstanding nature of her tinnitus or by another reason as yet undetermined.

Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms.

The objective of this study was to investigate functional deficits and reactive peri-tumoral brain plasticity events in glioma-bearing rats. 9L gliosarcoma cells were implanted into the forelimb region of the sensorimotor cortex in Fischer rats. Control animals underwent the same operation without tumor implantation. Sensitive tests for detecting sensorimotor dysfunction, including forelimb-use asymmetry, somatosensory asymmetry, and vibrissae-evoked forelimb placing tests, were conducted. We found that tumor-bearing animals exhibited significant composite behavioral deficits on day 14 post-tumor injection compared to surgical controls. With the assistance of magnetic resonance imaging, we demonstrated a significant correlation between tumor volume and magnitude of somatosensory asymmetry, indicating that the somatosensory asymmetry test can provide an effective and efficient means to measure and predict tumor progression. Histopathological assessments were performed after the rats were sacrificed 14 days following tumor implantation. Immunostaining revealed that densities of microtubule-associated protein 2, glial fibrillary acid protein, von Willebrand factor, and synaptophysin were all significantly upregulated in the peri-tumoral area, compared to the corresponding region in surgical controls, suggesting synaptic plasticity, astrocyte activation and angiogenesis in response to tumor insult. Understanding the behavioral and bystander cellular events associated with tumor progression may lead to improved evaluation and development of new brain tumor treatments that promote, or at least do not interfere with, functional adaptation.

A retrospective analysis of the effect of general anesthetics on the successful detection of interictal epileptiform activity in magnetoencephalography.

BACKGROUND: A magnetoencephalography (MEG) study requires the patient to lie still for a prolonged period of time. In children and uncooperative adults with epilepsy, general anesthesia or sedation may be required to insure a good quality study. As general anesthetics have anticonvulsant and proconvulsant properties, we investigated whether the use of anesthesia reduced the successful detection of interictal epilepsy activity. METHODS: MEG testing was performed on 41 epilepsy patients (10 women, 31 men; 1-48 yr) while anesthetized. To determine the impact of anesthesia on the identification of epileptiform activity, the anesthesia group of patients was compared with all other patients with epilepsy who were recorded in our laboratory without anesthesia, as well as with a subgroup of children with epilepsy who were able to be recorded without the need for anesthesia. RESULTS: Propofol was used in 38 patients, etomidate in two, and one received sevoflurane. Twenty-nine (71%) were found to have interictal epileptiform activity in their MEG results. The percentage of MEG studies with a positive yield for interictal epileptiform activity is comparable with the percentage (63%) found in the patients with epilepsy undergoing MEG without anesthesia. In the 38 children younger than 18 yr, 28 (74%) had interictal epileptiform activity compared with 80% done without anesthesia. CONCLUSION: We conclude that levels of anesthesia needed to provide unconsciousness and immobility during MEG studies do not significantly alter the likelihood of recording interictal epileptiform spike activity with MEG.

Magnetoencephalographic localization of the basal temporal language area.

Magnetoencephalography (MEG) recordings were made on 25 native English-speaking patients with localization-related epilepsy during a semantic language task (verb generation). Eighteen right-handed subjects with normal reading ability had MEG scans performed during the same language task. MEG data was analyzed by MR-FOCUSS, a current density imaging technique. Detectable MEG signals arising from activation in the left fusiform gyrus, also known as the basal temporal language area (BTLA), occurred at 167 +/- 18 ms (n = 43) in all subjects. The BTLA has been associated with a variety of language production and comprehension tasks involving processing of semantic, orthographic, and phonologic information. MEG may become an important tool in efforts to further define the linguistic operations of specific regions within this language area.

Language laterality determined by MEG mapping with MR-FOCUSS.

Magnetoencephalography recordings were made on 27 patients with localization related epilepsy during two different language tasks involving semantic and phonological processing (verb generation and picture naming). These patients underwent the semi-invasive intracarotid amobarbital procedure (IAP), also referred to as the Wada test, to determine the language-dominant hemisphere. Magnetoencephalography (MEG) data were analyzed by MR-FOCUSS, a current density imaging technique. A laterality index (LI) was calculated from this solution to determine which hemisphere had more neural activation during these language tasks. The LIs for three separate latencies, within each language task, were calculated to determine the latency that correlated best with each patient's IAP result. The LI for all language processing was calculated for the interval 150-550 ms, the second LI was calculated for the interval 230-290 ms (Wernicke's activation), and the third LI was calculated for the interval 396-460 ms (Broca's activation). In 23 of 24 epilepsy patients with a successful IAP, the LIs for Broca's activation, during the picture naming task, were in agreement with the results of the IAP (96% agreement). One of three patients who had an undetermined or bilateral IAP had an LI calculated for Broca's activation (396-460 ms) that agreed with intracranial mapping and clinical testing. These results indicate an 89% agreement rate (24 of 27) for magnetoencephalographic LI determination of the hemisphere of language dominance.

Cortical hyperexcitability in migraine patients before and after sodium valproate treatment.

DC-magnetoencephalography (DC-MEG)waveforms arising during migraine aura were used to determine the effectiveness of prophylactic medication therapy on neuronal hyperexcitability. Nine patients were prescribed valproate (Depakote) for migraine prophylaxis. MEG scans were recorded during visual stimulation before commencing medication and again after 30 days of daily use of valproate. Cortical brain activity was recorded during stimulation with a black-and-white circular checkerboard pattern alternating at 8 Hz and were analyzed with MR-FOCUSS. Large-amplitude DC-MEG signals, imaged to extended areas of occipital cortex, were seen before therapy. After 30 days of prophylactic treatment, reduced DC-MEG shifts in the occipital cortex and reduced incidence of migraine attacks were observed. Using visual stimulation, the authors demonstrated the hyperexcitability of widespread regions throughout occipital cortex in migraine patients, explaining the susceptibility for triggering spreading cortical depression and migraine aura. This study confirms that MEG can noninvasively determine the status of neuronal excitability before and after therapy. This finding may be helpful in determining which prophylactic medications will be most effective in reducing hyperexcitability in particular patients.

Magnetoencephalographic validation parameters for clinical evaluation of interictal epileptic activity.

The authors demonstrate that the confidence volume (the spatial volume that encompasses the 95% probability of source localization) of the single equivalent current dipole is helpful in validating magnetoencephalographic epileptic spike mapping. Such mapping involves distinguishing spikes from other neuronal events. The usual criteria for validating dipole fit reliability involve four parameters-correlation coefficient (R > or =0.98), goodness of fit (> or =0.95), root mean square magnetic field value (>400 fT), and dipole moment (Q value > 200 nAm)-but other parameters (direction of dipole moment, location of dipole, and confidence volume) can be considered. In 21 patients with epilepsy, the average correlation coefficient for 608 epileptic spikes was 0.99; average goodness of fit, 0.98; average root mean square, 1,198 fT; and the average Q value, 370 nAm. The mean average confidence volume was 0.30 +/- 0.27 cm3. Correlation coefficient values for quiet brain activity were less than 0.90; goodness of fit values, less than 0.85; and confidence volumes were large (>5 cm3); and for noise runs (no subject) they were even larger (>100 cm3), although correlation coefficient values were more than 0.80 and goodness of fit values were more than 0.85. Confidence volumes for noise data are large-for background brain activity even larger-but confidence volumes for epileptic spikes are small. Confidence volume, in conjunction with other parameters, may be a robust parameter for spike selection.