Neuromagnetic representation of musical roundness in chord progressions.

Introduction: Musical roundness perception relies on consonance/dissonance within a rule-based harmonic context, but also on individual characteristics of the listener. The present work tackles these aspects in a combined psychoacoustic and neurophysiological study, taking into account participant's musical aptitude. Methods: Our paradigm employed cadence-like four-chord progressions, based on Western music theory. Chord progressions comprised naturalistic and artificial sounds; moreover, their single chords varied regarding consonance/dissonance and harmonic function. Thirty participants listened to the chord progressions while their cortical activity was measured with magnetoencephalography; afterwards, they rated the individual chord progressions with respect to their perceived roundness. Results: Roundness ratings differed according to the degree of dissonance in the dominant chord at the progression's third position; this effect was pronounced in listeners with high musical aptitude. Interestingly, a corresponding pattern occurred in the neuromagnetic N1m response to the fourth chord (i.e., at the progression's resolution), again with somewhat stronger differentiation among musical listeners. The N1m magnitude seemed to increase during chord progressions that were considered particularly round, with the maximum difference after the final chord; here, however, the musical aptitude effect just missed significance. Discussion: The roundness of chord progressions is reflected in participant's psychoacoustic ratings and in their transient cortical activity, with stronger differentiation among listeners with high musical aptitude. The concept of roundness might help to reframe consonance/dissonance to a more holistic, gestalt-like understanding that covers chord relations in Western music.

Altered binaural hearing in pre-ataxic and ataxic mutation carriers of spinocerebellar ataxia type 3.

Brainstem degeneration is a prominent feature of spinocerebellar ataxia type 3 (SCA3), involving structures that execute binaural synchronization with microsecond precision. As a consequence, auditory processing may deteriorate during the course of disease. We tested whether the binaural "Huggins pitch" effect is suitable to study the temporal precision of brainstem functioning in SCA3 mutation carriers. We expected that they would have difficulties perceiving Huggins pitch at high frequencies, and that they would show attenuated neuromagnetic responses to Huggins pitch. The upper limit of Huggins pitch perception was psychoacoustically determined in 18 pre-ataxic and ataxic SCA3 mutation carriers and in 18 age-matched healthy controls. Moreover, the cortical N100 response following Huggins pitch onset was acquired by means of magnetoencephalography (MEG). MEG recordings were analyzed using dipole source modeling and comprised a monaural pitch condition and a no-pitch condition with simple binaural correlation changes. Compared with age-matched controls, ataxic but not pre-ataxic SCA3 mutation carriers had significantly lower frequency limits up to which Huggins pitch could be heard. Listeners with lower frequency limits also showed diminished MEG responses to Huggins pitch, but not in the two control conditions. Huggins pitch is a promising tool to assess brainstem functioning in ataxic SCA3 patients. Future studies should refine the psychophysiological setup to capture possible performance decrements also in pre-ataxic mutation carriers. Longitudinal observations will be needed to prove the potential of the assessment of Huggins pitch as a biomarker to track brainstem functioning during the disease course in SCA3.

Neuromagnetic representation of melodic contour processing in human auditory cortex.

The pattern of ups and downs in a sequence with varying pitch can be heard as a melodic contour. Contrary to single pitch, the neural representation of melodic contour information in the auditory cortex is rarely investigated, and it is not clear whether the processing entails a hemispheric asymmetry. The present magnetoencephalography study assessed the neuromagnetic responses of N = 18 normal-hearing adults to four-note sequences with fixed vs. varying pitch that were presented either monaurally or diotically; data were analyzed using minimum-norm reconstructions. The first note of the sequences elicited prominent transient activity in posterior auditory regions (Planum temporale), especially contralateral to the ear of entry. In contrast, the response to the subsequent notes originated from more anterior areas (Planum polare) and was larger for melodic contours than for fixed pitch sequences, independent from the ear of entry and without hemispheric asymmetry. Together, the results point to a gradient in the early cortical processing of melodic contours, both in spatial and functional terms, where posterior auditory activity reflects the onset of a pitch sequence and anterior activity reflects its subsequent notes, including the difference between sequences with fixed pitch and melodic contours.

Early cortical processing of pitch height and the role of adaptation and musicality.

Pitch is an important perceptual feature; however, it is poorly understood how its cortical correlates are shaped by absolute vs relative fundamental frequency (f0), and by neural adaptation. In this study, we assessed transient and sustained auditory evoked fields (AEFs) at the onset, progression, and offset of short pitch height sequences, taking into account the listener's musicality. We show that neuromagnetic activity reflects absolute f0 at pitch onset and offset, and relative f0 at transitions within pitch sequences; further, sequences with fixed f0 lead to larger response suppression than sequences with variable f0 contour, and to enhanced offset activity. Musical listeners exhibit stronger f0-related AEFs and larger differences between their responses to fixed vs variable sequences, both within sequences and at pitch offset. The results resemble prominent psychoacoustic phenomena in the perception of pitch contours; moreover, they suggest a strong influence of adaptive mechanisms on cortical pitch processing which, in turn, might be modulated by a listener's musical expertise.

Transient and sustained processing of musical consonance in auditory cortex and the effect of musicality.

In recent years, electroencephalography and magnetoencephalography (MEG) have both been used to investigate the response in human auditory cortex to musical sounds that are perceived as consonant or dissonant. These studies have typically focused on the transient components of the physiological activity at sound onset, specifically, the N1 wave of the auditory evoked potential and the auditory evoked field, respectively. Unfortunately, the morphology of the N1 wave is confounded by the prominent neural response to energy onset at stimulus onset. It is also the case that the perception of pitch is not limited to sound onset; the perception lasts as long as the note producing it. This suggests that consonance studies should also consider the sustained activity that appears after the transient components die away. The current MEG study shows how energy-balanced sounds can focus the response waves on the consonance-dissonance distinction rather than energy changes and how source modeling techniques can be used to measure the sustained field associated with extended consonant and dissonant sounds. The study shows that musical dyads evoke distinct transient and sustained neuromagnetic responses in auditory cortex. The form of the response depends on both whether the dyads are consonant or dissonant and whether the listeners are musical or nonmusical. The results also show that auditory cortex requires more time for the early transient processing of dissonant dyads than it does for consonant dyads and that the continuous representation of temporal regularity in auditory cortex might be modulated by processes beyond auditory cortex.NEW & NOTEWORTHY We report a magnetoencephalography (MEG) study on transient and sustained cortical consonance processing. Stimuli were long-duration, energy-balanced, musical dyads that were either consonant or dissonant. Spatiotemporal source analysis revealed specific transient and sustained neuromagnetic activity in response to the dyads; in particular, the morphology of the responses was shaped by the dyad's consonance and the listener's musicality. Our results also suggest that the sustained representation of stimulus regularity might be modulated by processes beyond auditory cortex.

Modeling and MEG evidence of early consonance processing in auditory cortex.

Pitch is a fundamental attribute of auditory perception. The interaction of concurrent pitches gives rise to a sensation that can be characterized by its degree of consonance or dissonance. In this work, we propose that human auditory cortex (AC) processes pitch and consonance through a common neural network mechanism operating at early cortical levels. First, we developed a new model of neural ensembles incorporating realistic neuronal and synaptic parameters to assess pitch processing mechanisms at early stages of AC. Next, we designed a magnetoencephalography (MEG) experiment to measure the neuromagnetic activity evoked by dyads with varying degrees of consonance or dissonance. MEG results show that dissonant dyads evoke a pitch onset response (POR) with a latency up to 36 ms longer than consonant dyads. Additionally, we used the model to predict the processing time of concurrent pitches; here, consonant pitch combinations were decoded faster than dissonant combinations, in line with the experimental observations. Specifically, we found a striking match between the predicted and the observed latency of the POR as elicited by the dyads. These novel results suggest that consonance processing starts early in human auditory cortex and may share the network mechanisms that are responsible for (single) pitch processing.

Limitations of Specific Coagulation Tests for Direct Oral Anticoagulants: A Critical Analysis.

Background During treatment with direct oral anticoagulants ( DOAC ), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay ( AXA ) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL ). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.

Neuromagnetic correlates of voice pitch, vowel type, and speaker size in auditory cortex.

Vowel recognition is largely immune to differences in speaker size despite the waveform differences associated with variation in speaker size. This has led to the suggestion that voice pitch and mean formant frequency (MFF) are extracted early in the hierarchy of hearing/speech processing and used to normalize the internal representation of vowel sounds. This paper presents a magnetoencephalographic (MEG) experiment designed to locate and compare neuromagnetic activity associated with voice pitch, MFF and vowel type in human auditory cortex. Sequences of six sustained vowels were used to contrast changes in the three components of vowel perception, and MEG responses to the changes were recorded from 25 participants. A staged procedure was employed to fit the MEG data with a source model having one bilateral pair of dipoles for each component of vowel perception. This dipole model showed that the activity associated with the three perceptual changes was functionally separable; the pitch source was located in Heschl's gyrus (bilaterally), while the vowel-type and formant-frequency sources were located (bilaterally) just behind Heschl's gyrus in planum temporale. The results confirm that vowel normalization begins in auditory cortex at an early point in the hierarchy of speech processing.

Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.

Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m.

Duifhuis pitch: neuromagnetic representation and auditory modeling.

When a high harmonic is removed from a cosine-phase harmonic complex, we hear a sine tone pop out of the perception; the sine tone has the pitch of the high harmonic, while the tone complex has the pitch of its fundamental frequency, f0. This phenomenon is commonly referred to as Duifhuis Pitch (DP). This paper describes, for the first time, the cortical representation of DP observed with magnetoencephalography. In experiment 1, conditions that produce the perception of a DP were observed to elicit a classic onset response in auditory cortex (P1m, N1m, P2m), and an increment in the sustained field (SF) established in response to the tone complex. Experiment 2 examined the effect of the phase spectrum of the complex tone on the DP activity: Schroeder-phase negative waves elicited a transient DP complex with a similar shape to that observed with cosine-phase waves but with much longer latencies. Following the transient DP activity, the responses of the negative and positive Schroeder-phase waves converged, and the increment in the SF slowly died away. In the absence of DP, the two Schroeder-phase conditions with low peak factors both produced larger SFs than cosine-phase waves with large peak factors. A model of the auditory periphery that includes coupling between adjacent frequency channels is used to explain the early neuromagnetic activity observed in auditory cortex.

Neuromagnetic representation of musical register information in human auditory cortex.

Pulse-resonance sounds like vowels or instrumental tones contain acoustic information about the physical size of the sound source (pulse rate) and body resonators (resonance scale). Previous research has revealed correlates of these variables in humans using functional neuroimaging. Here, we report two experiments that use magnetoencephalography to study the neuromagnetic representations of pulse rate and resonance scale in human auditory cortex. In Experiment 1, auditory evoked fields were recorded from nineteen subjects presented with French horn tones, the pulse rate and resonance scale of which had been manipulated independently using a mucoder. In Experiment 2, fifteen subjects listened to French horn tones which differed in resonance scale but which lacked pulse rate cues. The resulting cortical activity was evaluated by spatio-temporal source analysis. Changes in pulse rate elicited a well-defined N1m component with cortical generators located at the border between Heschl's gyrus and planum temporale. Changes in resonance scale elicited a second, independent, N1m component located in planum temporale. Our results demonstrate that resonance scale can be distinguished in its neuromagnetic representation from cortical activity related to the sound's pulse rate. Moreover, the existence of two separate components in the N1m sensitive to register information highlights the importance of this time window for the processing of frequency information in human auditory cortex.

EEG power spectrum to predict prognosis after hemicraniectomy for space-occupying middle cerebral artery infarction.

BACKGROUND: Early prediction of outcome after decompressive surgery for space-occupying middle cerebral artery (MCA) infarction is needed to guide further therapy. Here we applied spectral EEG analysis to determine the prognosis early after hemicraniectomy, while the patient is still treated in the intensive care unit. METHODS: Continuous EEG monitoring following hemicraniectomy was performed in 10 patients with space-occupying MCA infarction. All patients were analgosedated and mechanically ventilated. The first 6 h of monitoring after surgery were evaluated by spectral analysis. Outcome measures included Glasgow Outcome Scale (GOS), Level of Consciousness Scale (LOC) and National Institute of Health Stroke Scale (NIHSS) at discharge. Outcome after 3 months was assessed by modified Rankin Scale. RESULTS: Six patients displayed a peak at 5-10 Hz in the EEG power spectrum. All these patients had a GOS score of 3 and an LOC score >or=7 at discharge. In contrast, the 4 patients without faster EEG activity had a GOS of 2 and LOC

Children with developmental language delay at 24 months of age: results of a diagnostic work-up.

The aim of this study was to evaluate if a diagnostic work-up should be recommended for 2-year-old children with developmental language delay (LD), or if the widely chosen 'wait and see' strategy is adequate. Children with LD were identified in paediatric practices during routine developmental check-ups using a German parent-report screening questionnaire (adapted from the MacArthur Communicative Development Inventories). A standardized German instrument and the Netherlands version of Bayley Scales of Infant Development (2nd ed.) were used to assess language ability and nonverbal cognitive development respectively in 100 children with LD (65 males, 35 females; mean age 24.7 mo [SD 0.9]) and a control group of 53 children with normal language development (33 males, 20 females; mean age 24.6 mo [SD 0.8]). Neurological and audiometric testing were also performed. Sixty-one per cent of the LD group had specific expressive LD and 17% specific receptive-expressive LD. In 22%, LD was associated with other neurodevelopmental problems, 6% showed significant deficits in nonverbal cognitive abilities, and in 12%, nonverbal cognitive abilities were borderline. Four per cent fulfilled the criteria of childhood autism. LD at 2 years proved to represent a sensitive marker for different developmental problems. Adequate early intervention requires a clear distinction between specific expressive or receptive-expressive LD and LD associated with other neurodevelopmental problems. Though catch-up development is to be expected in a substantial proportion of 'late talkers', our data demonstrate that a general 'wait and see' approach is not justified in young children with LD. A proposal for a rational diagnostic work-up is presented.

Representation of auditory-filter phase characteristics in the cortex of human listeners.

Harmonic tone complexes with component phases, adjusted using a variant of a method proposed by Schroeder, can produce pure-tone masked thresholds differing by >20 dB. This phenomenon has been qualitatively explained by the phase characteristics of the auditory filters on the basilar membrane, which differently affect the flat envelopes of the Schroeder-phase maskers. We examined the influence of auditory-filter phase characteristics on the neural representation in the auditory cortex by investigating cortical auditory evoked fields (AEFs). We found that the P1m component exhibited larger amplitudes when a long-duration tone was presented in a repeating linearly downward sweeping (Schroeder positive, or m(+)) masker than in a repeating linearly upward sweeping (Schroeder negative, or m(-)) masker. We also examined the neural representation of short-duration tone pulses presented at different temporal positions within a single period of three maskers differing in their component phases (m(+), m(-), and sine phase m(0)). The P1m amplitude varied with the position of the tone pulse in the masker and depended strongly on the masker waveform. The neuromagnetic results in all cases were consistent with the perceptual data obtained with the same stimuli and with results from simulations of neural activity at the output of cochlear preprocessing. These findings demonstrate that phase effects in peripheral auditory processing are accurately reflected up to the level of the auditory cortex.

Auditory temporal resolution in children assessed by magnetoencephalography.

By means of magnetoencephalography we investigated the auditory-evoked fields (AEFs) elicited by broadband noise bursts in a gap-detection paradigm in children. AEFs of 16 healthy children (mean age 8.7 years) were recorded while they passively listened to 100-ms white-noise bursts with temporal gaps of 3, 6, 10 and 30 ms inserted after 5 or 50 ms. The peak of the earliest and largest positivity occurred at 97 ms and was evaluated by spatiotemporal source analysis. Psychophysical gap-detection thresholds were obtained for the same children. We found that the neuromagnetic gap responses corresponded to the psychoacoustic thresholds. AEFs thus provide an objective tool to assess auditory temporal resolution in children. Children's neuromagnetic response patterns differed significantly from the adult responses under the same experimental conditions.

Latency effect of the pitch response due to variations of frequency and spectral envelope.

OBJECTIVE: A clear definition of pitch and timbre is still an open debate and often both terms are mixed up in investigations of tone height. However, fundamental frequency (f(0)) and spectral envelope of a sound play a major role in the perception of tone height. Recent electrophysiological experiments showed that one sub-component of the complex N 100-signal was found to be highly correlated to the perceived tone height. METHODS: Tone height was independently varied by both, a change of f(0) and spectral envelope in order to disentangle the influence of both parameters. Relative tone height was determined psychoacoustically. Neuromagnetic responses were evaluated using source-analysis. RESULTS: Perceived tone height increases with increasing f(0) or spectral envelope. Latency of the pitch change response (PCR) reacts oppositely for the two modi of tone height change. For increasing f(0) and fixed bandpass condition, tone height increases and the latency of the PCR decreases. In contrast, for increasing the center frequency of the bandpass with fixed f(0), tone height increases, but the latency of the PCR increases. CONCLUSIONS: The neuromagnetic pitch response is influenced by both, f(0) and spectral envelope. SIGNIFICANCE: Further investigations of the influence of pitch and timbre on neurophysiological pitch responses have to take into account that both, f(0) and spectral envelope, affect tone height and latency of the PCR.

Neuromagnetic correlates of streaming in human auditory cortex.

The brain is constantly faced with the challenge of organizing acoustic input from multiple sound sources into meaningful auditory objects or perceptual streams. The present study examines the neural bases of auditory stream formation using neuromagnetic and behavioral measures. The stimuli were sequences of alternating pure tones, which can be perceived as either one or two streams. In the first experiment, physical stimulus parameters were varied between values that promoted the perceptual grouping of the tone sequence into one coherent stream and values that promoted its segregation into two streams. In the second experiment, an ambiguous tone sequence produced a bistable percept that switched spontaneously between one- and two-stream percepts. The first experiment demonstrated a strong correlation between listeners' perception and long-latency (>60 ms) activity that likely arises in nonprimary auditory cortex. The second demonstrated a covariation between this activity and listeners' perception in the absence of physical stimulus changes. Overall, the results indicate a tight coupling between auditory cortical activity and streaming perception, suggesting that an explicit representation of auditory streams may be maintained within nonprimary auditory areas.

Neuromagnetic responses reflect the temporal pitch change of regular interval sounds.

The pitch onset response (POR) evoked by the transition between two regular interval sounds (RIS) with different pitch was studied by recording the neuromagnetic responses with a 122-channel whole head magnetoencephalograph (MEG). The parameters of RIS were varied giving rise to characteristic changes in the latency of the first prominent deflection occurring about 100 to 140 ms after the transition. These latency differences of the neurophysiological signal correlated strongly with the psychoacoustic findings obtained from the same individuals. Some of the observed changes cannot be explained by obvious physical differences as changes in the spectrum, but only by temporal processing mechanisms as the auditory image model (Patterson, R.D., Allerhand, M., Giguere, C., 1995. Time-domain modelling of peripheral auditory processing: a modular architecture and a software platform. J. Acoust. Soc. Am. 98, 1890-1894). The location of the POR evoked by the transition was found to be in lateral Heschl's Gyrus, which gives further evidence that this is the center of processing pitch changes in the auditory cortex.

Middle latency auditory-evoked fields reflect psychoacoustic gap detection thresholds in human listeners.

The resolution of the temporal processing in the primary auditory cortex (PAC) was studied in human listeners by using temporal gaps of 3, 6, 10, and 30 ms inserted in 100-ms noise bursts. Middle latency auditory-evoked fields (MAEFs) were recorded and evaluated by spatio-temporal source analysis. The dependency of the neurophysiological activation at about 37 ms (P37m) on the temporal position of the gap was investigated by inserting silent periods 5, 20, and 50 ms after noise burst onset. The morphology of the waveforms evoked by the gap showed that the MAEFs were largely determined by the on-response to the noise burst following the gap. The comparison of the source waveforms revealed two major effects: 1) the amplitudes of the MAEFs increased with longer gap durations and 2) the amplitudes increased with the length of the leading noise burst. When the gap was inserted after 50 ms, a significant deflection of the collapsed left and right hemisphere data was observed for all gap durations. The P37m amplitude failed to reach significance for the shortest gap duration of 3 ms when the gap occurred after 20 and 5 ms. These neuromagnetically derived minimum detectable gap responses closely resembled psychoacoustic thresholds obtained from the same subjects (leading noise burst, 50 ms: 2.4 ms; 20 ms: 3.2; and 5 ms: 5.3 ms). The correspondence between psychoacoustic thresholds and the cortical activation indicates that the recording of MAEFs provides an objective and noninvasive tool to assess cortical temporal acuity.

EEG and MEG source analysis of single and averaged interictal spikes reveals intrinsic epileptogenicity in focal cortical dysplasia.

PURPOSE: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre- and postoperative anatomic magnetic resonance imaging (MRI). PATIENTS: We studied nine children and adolescents (age, 3.5-15.9 years) with localization-related epilepsy and FCD diagnosis based on MRI. Five patients underwent epilepsy surgery, two of them after long-term recording with subdural grid electrodes, and one after intraoperative electrocorticography. METHODS: The 122-channel whole-head MEGs and 33-channel EEGs were recorded simultaneously for 25 to 40 min. Interictal spikes were identified visually and used as templates to search for similar spatiotemporal spike patterns throughout the recording. With the BESA program, similar spikes (r > 0.85) were detected, averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal source analysis with a multishell spherical head model. Peak activity from single spikes was modeled by single dipoles for the same subset of spikes. Source localization was visualized by superposition on T1-weighted MRI and compared with the lesion identified in T1- and T2-weighted MRI. In the five cases undergoing epilepsy surgery, the results were correlated with invasive recordings, postoperative MRI, and outcome. RESULTS: In all cases, the analysis of averaged spikes showed a localization of onset- and peak-related sources within the visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284) were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91% localized within the lesion with MEG, and 93.5% with EEG. In three of five patients operated on, the resected area included the onset zones of averaged EEG and MEG spike activity. These patients had excellent postoperative outcome, whereas the others did not become seizure free. CONCLUSIONS: Consistent MEG and EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic epileptogenicity in FCD.