Multimodal imaging of functional networks and event-related potentials in performance monitoring.

The stop-signal task is a prototypical experiment to study cognitive processes that mediate successful performance in a rapidly changing environment. By means of simultaneous recording and combined analysis of electroencephalography and functional magnetic resonance imaging on single trial level, we provide a comprehensive view on brain responses related to performance monitoring in this task. Three types of event-related EEG components were analyzed: a go-related N2/P3-complex devoid of motor-inhibition, the stop-related N2/P3-complex and the error-related negativity with its consecutive error positivity. Relevant functional networks were identified by crossmodal correlation analyses in a parallel independent component analysis framework. Go-related potentials were associated with a midcingulate network known to participate in the processing of conflicts, a left-dominant somatosensory-motor network, and deactivations in visual cortices. Stop-related brain responses in association with the N2/P3-complex were seen with networks known to support motor and cognitive inhibition, including parts of the basal ganglia, the anterior midcingulate cortex and pre-supplementary motor area as well as the anterior insula. Error-related brain responses showed a similar constellation with additional recruitment of the posterior insula and the inferior frontal cortex. Our data clearly indicate that the pre-supplementary motor area is involved in inhibitory mechanisms but not in the processing of conflicts per se.

The role of the cingulate cortex as neural generator of the N200 and P300 in a tactile response inhibition task.

Both the N200 and P300, which are, for example, evoked by Go/Nogo or Stop-Signal tasks, have long been interpreted as indicators for inhibition processes. Such interpretations have recently been challenged, and interest in the exact neural generators of these brain responses is continuously growing. Using recent methodological advancements, source estimations for the N200 and P300 as evoked by a tactile response inhibition task were computed. Current density reconstructions were also calculated accounting for interindividual differences in head geometry by incorporating information from T1-weighted magnetic resonance images. To ease comparability with relevant paradigms, the task was designed to mimic important characteristics of both Go/Nogo and Stop-Signal tasks as prototypes for a larger set of paradigms probing response inhibition. A network of neural generators was revealed, which has previously been shown to act in concert with executive control processes and thus is in full agreement with observations from other modalities. Importantly, a spatial segregation of midcingulate sources was observed. Our experimental data indicate that a left anterior region of the midcingulate cortex (MCC) is a major neural generator of the N200, whereas the midcingulate generator of the P300 is located in the right posterior MCC. Analyses of the P300 also revealed several areas, which have previously been associated with motor functions, for example, the precentral region. Our data clearly suggest a neuroanatomical and therefore also functional dissociation of the N200 and P300, a finding that cannot easily be provided by other imaging techniques.

[Magnetoencephalography in psychiatry]. / Magnetoenzephalographie in der Psychiatrie.

Neuropsychiatric disorders usually come with only sublime structural changes. Functional imaging can point at specific disturbances in information processing in neural networks. Besides imaging of receptor and metabolic functions with PET and fMRI, electromagnetic methods such as electroencephalography (EEG) and magnetoencephalography (MEG) offer the possibility for imaging of dynamic dysfunctions. As compared to EEG, MEG has a shorter history and is less common despite offering considerable advantages in temporospatial resolution and sensitivity to detect impaired signal processing and network functioning which renders it particularly interesting for psychiatric applications. Disturbed processing in the auditory and visual domain emerging in schizophrenic, affective and anxiety disorders can be detected with high sensitivity. Moreover, the neuromagnetic baseline activity allows conclusions to be drawn regarding neural network functions. Due to its high sensitivity to single deficits in information processing and to pharmacological effects, MEG will achieve clinical significance in specific areas.

Tonotopic organization of the auditory cortex: pitch versus frequency representation.

According to the place principles of the classical hearing theory, the physical entity frequency is encoded in the auditory periphery as place information (tonotopic representation), which is decoded in more central parts of the auditory system to form the subjective entity pitch. However, this relation is true only for pure-tone signals (spectral pitch); it can be quite different in the case of complex auditory stimuli (virtual pitch), thus requiring a multistage process for pitch formation. Neuromagnetic measurements showed that the tonotopic organization of the primary auditory cortex reflects the pitch rather than the frequency of the stimulus; that is, the pitch formation process must take place in subcortical regions.

Increased cortical representation of the fingers of the left hand in string players.

Magnetic source imaging revealed that the cortical representation of the digits of the left hand of string players was larger than that in controls. The effect was smallest for the left thumb, and no such differences were observed for the representations of the right hand digits. The amount of cortical reorganization in the representation of the fingering digits was correlated with the age at which the person had begun to play. These results suggest that the representation of different parts of the body in the primary somatosensory cortex of humans depends on use and changes to conform to the current needs and experiences of the individual.

Local sphere-based co-registration for SAM group analysis in subjects without individual MRI.

Synthetic aperture magnetometry (SAM) is a powerful MEG source localization method to analyze evoked as well as induced brain activity. To gain structural information of the underlying sources, especially in group studies, individual magnetic resonance images (MRI) are required for co-registration. During the last few years, the relevance of MEG measurements on understanding the pathophysiology of different diseases has noticeable increased. Unfortunately, especially in patients and small children, structural MRI scans cannot always be performed. Therefore, we developed a new method for group analysis of SAM results without requiring structural MRI data that derives its geometrical information from the individual volume conductor model constructed for the SAM analysis. The normalization procedure is fast, easy to implement and integrates seamlessly into an existing landmark based MEG-MRI co-registration procedure. This new method was evaluated on different simulated points as well as on a pneumatic index finger stimulation paradigm analyzed with SAM. Compared with an established MRI-based normalization procedure (SPM2) the new method shows only minor errors in single subject results as well as in group analysis. The mean difference between the two methods was about 4 mm for the simulated as well as for finger stimulation data. The variation between individual subjects was generally higher than the error induced by the missing MRIs. The method presented here is therefore sufficient for most MEG group studies. It allows accomplishing MEG studies with subject groups where MRI measurements cannot be performed.

Neural interactions within and beyond the critical band elicited by two simultaneously presented narrow band noises: a magnetoencephalographic study.

Neural activities elicited in the auditory system are systematically organized according to the frequency characteristics of corresponding sound inputs. This systematic frequency alignment, called 'tonotopy,' plays an important role in auditory perception. By means of magnetoencephalography (MEG) we investigated here interactions between neural groups activated by two simultaneously presented narrow-band noises (NBNs) within the human cortical tonotopic map. Auditory evoked fields indicated that the neural interactions activated by these NBNs depended on the frequency difference between them: the amplitude of the N1m-response systematically increased with increasing frequency difference between the NBNs until the critical bandwidth was reached. In contrast, the N1m decreased with frequency difference exceeding the critical bandwidth. The different N1m-response patterns within and beyond the critical band seem to result from the combination of inhibitory and excitatory neural processes in the auditory pathway and may contribute to the perception of complex sound patterns like speech and music.

Inhibition-induced plasticity in tinnitus patients after repetitive exposure to tailor-made notched music.

OBJECTIVE: Notch-filtered music has been shown to induce frequency-specific inhibition. Here, we investigated which cortical structures are affected by tailor-made notched music (TMNM) in tinnitus patients and how this inhibition-induced plasticity develops over time. METHODS: Nine subjects suffering from chronic tonal tinnitus listened to music passing through a notch-filter centered at the patient's individual tinnitus frequency (TMNM) for three hours on three consecutive days. Before and after each listening session, a tone at the tinnitus frequency and a control tone of 500 Hz were presented in the magnetoencephalograph. Subjective tinnitus loudness was measured via visual analog scales. RESULTS: TMNM exposure reduced subjective tinnitus loudness and neural activity evoked by the tinnitus tone in temporal, parietal and frontal regions within the N1m time interval. Reduction of temporal and frontal activation correlated significantly with tinnitus loudness decline. Reduction of tinnitus related neural activity persisted and accumulated over three days. CONCLUSIONS: Inhibition-induced plasticity occurs in a cortical network, known to be crucial for tinnitus perception. This cortical reorganization evolves fast and accumulates across sessions. SIGNIFICANCE: This study extends previous work on inhibition-induced plasticity, as it demonstrates the involvement of parietal and frontal areas and discovers a cumulative effect of cortical reorganization in tinnitus patients.

Atypical organisation of the auditory cortex in dyslexia as revealed by MEG.

Neuroanatomical and -radiological studies have converged to suggest an atypical organisation in the temporal bank of the left-hemispheric Sylvian fissure for dyslexia. Against the background of this finding, we applied high temporal resolution magnetoencephalography (MEG) to investigate functional aspects of the left-hemispheric auditory cortex in 11 right-handed dyslexic children (aged 8-13 years) and nine matched normal subjects (aged 8-14 years). Event-related field components during a passive oddball paradigm with pure tones and consonant-vowel syllables were evaluated. The first major peak of the auditory evoked response, the M80, showed identical topographical distributions in both groups. In contrast, the generating brain structures of the later M210 component were located more anterior to the earlier response in children with dyslexia only. Control children exhibited the expected activation of more posterior source locations of the component that appeared later in the processing stream. Since the group difference in the relative location of the M210 source seemed to be independent of stimulus category, it is concluded that dyslexics and normally literate children differ as to the organisation of their left-hemispheric auditory cortex.

Representational cortex in musicians. Plastic alterations in response to musical practice.

The lifelong ability to adapt to environmental needs is based on the capacity of the central nervous system for plastic alterations. In a series of neurophysiological experiments, we studied the impact of music and musical training in musicians on the specific functional organization in auditory and somatosensory representational cortex. In one such study, subjects listened to music from which one specific spectral frequency was removed. This led to rapid and reversible adaptation of neuronal responses in auditory cortex. Further experimental evidence demonstrated that long years of practice and training by professional musicians to enable them to reach their capacity is associated with enlarged cortical representations in the somatosensory and auditory domains. This tuning of neuronal representations was specifically observed for musical tones and was absent when pure sinusoidal tones were used as stimuli. In the somatosensory cortex, plastic changes proved to be specific for the fingers frequently used and stimulated. These changes were not detected in the fingers of the hand that were not involved in playing the particular instrument. Neuroplastic alterations also may be driven into a domain where they may become maladaptive. The clinical syndrome of focal hand dystonia that may occur in musicians who engage in forceful practice may be one such consequence. We will discuss the possibilities of reversing maladaptive responses leading to the successful treatment of focal hand dystonia, which relies on basic research about cortical reorganization. This example elucidates how neuroscientific progress can guide the development of practice guidelines and therapeutic measures for the benefit of professional musicians.

Oscillatory neuromagnetic activity induced by language and non-language stimuli.

Event-related oscillatory brain activity during language perception differs from activity occurring during the processing of comparable non-language stimuli. This fact became apparent in the observation of changes in the normalized spectral power of magnetoencephalographic (MEG) signals during the subject's processing of these stimuli. MEG was recorded over the left and right hemispheres of 12 right-handed subjects. During the experimental session, bisyllablic content words and physically similar non-language stimuli were presented with equal probability in a randomized order in either the visual or auditory modality. Approximately 15% of these stimuli were marked and the subject's task was to detect these marked stimuli. As a major characteristic of language vs. non-language processing, we obtained an enhancement of the normalized spectral power around 240 ins in the 60-65-Hz band over the left hemisphere for the language condition and over the right hemisphere for the non-language condition, independent of the modality of stimulus presentation. Starting at approximately the same latency but in lower-frequency bands (15-45-Hz), an extended (250-600 ms) reduction of normalized spectral power was observed. This reduction, although it generally confirmed previous results, differed in the no hemisphere-specific reduction was found for the processing of words. A domain-specific enhancement of normalized spectral power was also evident around 800-1200 ms in the 15-30-Hz band. In the auditory condition, this enhancement of the normalized spectral power was larger after the presentation of language stimuli whereas in the visual condition a larger enhancement of the normalized spectral power was obtained after presentation of non-language stimuli. As this latter effect appears relatively late after the stimulus onset and differs in expression for both modalities of stimulus presentation, a simple relationship between language perception and oscillatory brain dynamics can be excluded for this enhancement. In contrast, the left hemispheric enhancement of the normalized spectral power present around 240 ms in the 60-65-Hz band seems to reflect oscillatory pattern specific to the processing of words.

Musicians with absolute pitch show distinct neural activities in the auditory cortex.

Meg responses from musicians who had absolute pitch and from non-musicians were measured while they received different auditory stimuli. The parameters of single equivalent current dipoles (ECDs) were calculated for the N1m responses occurring in the auditory cortex. The location of the ECD for the noise burst was significantly posterior to the ECDs for the tones in the two hemispheres of the musicians, but not for those of the non-musicians. Further, in the left hemisphere the ECDs for the musicians were significantly posterior to those for the non-musicians. These results suggest distinct neural activities in the auditory cortex of musicians, which may be the result of cortical plasticity produced by training and/or an inherent cortical structural specificity.

Brain stem auditory evoked fields in response to clicks.

Magnetoencephalographic correlates of brain stem auditory evoked potentials (BAEP) have been identified by applying the model of a current dipole with invariant location and orientation (fixed dipole) to data recorded with a 37-channel first-order gradiometer system. In all three subjects studied, the dominating wave of the recorded brain stem auditory evoked field (BAEF) coincided exactly with wave V in the contralateral BAEP (maximal field amplitude of the order of 2-3 fT). In one subject, also a wave preceding wave V was observed, which was associated with basically the same spatial pattern as wave V itself, but had an opposite polarity. The study suggests that the supplementary information provided by BAEF measurements could be decisive for a better understanding of human auditory evoked brain stem activity.

Plastic changes in the auditory cortex induced by intensive frequency discrimination training.

The slow auditory evoked (wave N1m) and mismatch field (MMF) elicited by sequences of pure tones of 1000 Hz and deviant tones of 1050, 1010 and 1005 Hz were measured before, during and 3 weeks after subjects were trained at frequency discrimination for 15 sessions (over 3 weeks) using an odd-ball procedure. The task of the subject was to detect deviants differing by progressively smaller frequency shifts from the standard stimulus. Frequency discrimination improved rapidly in the first week and was followed by small but constant improvements thereafter. N1m and MMF responses to the deviant stimuli increased in amplitude during training. This enhancement persisted until training was finished, but decreased 3 weeks later. The results suggest a plastic reorganization of the cortical representation for the trained frequencies.

Combined EEG and MEG recordings of visual 40 Hz responses to illusory triangles in human.

EEG and MEG were simultaneously recorded to study the visual gamma-band (30-70 Hz) responses. The electrical gamma-band response phase-locked to stimulus onset can be subdivided into a central component at 39 Hz and an occipital component at 36 Hz. A new high-frequency magnetic phase-locked response recorded over the occipital lobe is described. Its topography is complex and probably reflects the activity of multiple sources. Both electrical and magnetic high-frequency responses differ in topography from the low-frequency responses in the same latency range, suggesting that at least partially distinct sources are involved. The existence of a non-phase-locked 40 Hz component around 280 ms is confirmed in EEG data but is not detectable in MEG data.

Timbre-specific enhancement of auditory cortical representations in musicians.

Neural imaging studies have shown that the brains of skilled musicians respond differently to musical stimuli than do the brains of non-musicians, particularly for musicians who commenced practice at an early age. Whether brain attributes related to musical skill are attributable to musical practice or are hereditary traits that influence the decision to train musically is a subject of controversy, owing to its pedagogic implications. Here we report that auditory cortical representations measured neuromagnetically for tones of different timbre (violin and trumpet) are enhanced compared to sine tones in violinists and trumpeters, preferentially for timbres of the instrument of training. Timbre specificity is predicted by a principle of use-dependent plasticity and imposes new requirements on nativistic accounts of brain attributes associated with musical skill.

Failure of dominant left-hemispheric activation to right-ear stimulation in schizophrenia.

Schizophrenia is associated with an absence of the lateralizations that typify the human brain. Previous evidence emphasized structural changes, particularly reduced asymmetry in extension and surface of the planum temporale, although gross structural deviations occur only in a minority of patients. The present study describes an absence of lateralization on a robust functional measure that characterized schizophrenia patients: healthy subjects but not schizophrenics displayed a contralateral left-hemispheric dominance of the auditory evoked magnetic field to right-ear auditory stimulation. Absence of contralateral dominance in response to auditory stimuli among schizophrenia patients may indicate a failure to establish unequivocal left-hemispheric dominance of the phonological loop as hypothesized by Crow.

Alteration of digital representations in somatosensory cortex in focal hand dystonia.

Focal hand dystonia involves a loss of motor control of one or more digits; it is associated with the repetitive, synchronous movements of the digits made by musicians over periods of many years. Magnetic source imaging revealed that there is a smaller distance (fusion) between the representations of the digits in somatosensory cortex for the affected hand of dystonic musicians than for the hands of non-musician control subjects. The data suggest that use-dependent susceptibility to digital representation fusion in cortex may be involved in the etiology of focal dystonia. A successful therapy for the condition has been developed based on this consideration.

Comparison of magnetic and metabolic brain activity during a verb generation task.

The magnetic and metabolic activational patterns of the brain during the perception, generation and silent articulation of words overlap to some extent, yet also measure concrete activational patterns. In the present study, auditory evoked magnetic fields (MEG) and changes in regional cerebral blood flow (PET) were examined in healthy subjects during a verb generation task. The aim of the study was to determine whether the advantages of both recording techniques can be combined so as to identify distributed sources of brain activity during particular tasks such as language processing. Given the currently observed disparity of the results from the two types of brain imaging we conclude that PET data will most likely not provide physiologically meaningful constraints for the distributed source analysis of MEG data, and may not necessarily validate results of distributed source analyses.

Short-term plasticity of the human auditory cortex.

Magnetoencephalographic measurements (MEG) were used to examine the effect on the human auditory cortex of removing specific frequencies from the acoustic environment. Subjects listened for 3 h on three consecutive days to music "notched" by removal of a narrow frequency band centered on 1 kHz. Immediately after listening to the notched music, the neural representation for a 1-kHz test stimulus centered on the notch was found to be significantly diminished compared to the neural representation for a 0.5-kHz control stimulus centered one octave below the region of notching. The diminished neural representation for 1 kHz reversed to baseline between the successive listening sessions. These results suggest that rapid changes can occur in the tuning of neurons in the adult human auditory cortex following manipulation of the acoustic environment. A dynamic form of neural plasticity may underlie the phenomenon observed here.