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.

Variations in midcingulate morphology are related to ERP indices of cognitive control.

The midcingulate cortex (MCC; often somewhat imprecisely referred to as dorsal or cognitive part of the anterior cingulate cortex or dACC) is a core region contributing to cognitive control. Neuroanatomical deviations in the midcingulate region have been observed in a variety of mental disorders. Even in healthy subjects a high degree of morphological variability is seen, for example concerning the degree of anterior midcingulate fissurization. To investigate the relationship between anterior midcingulate morphology and function, individuals with a leftward midcingulate folding asymmetry (LEFT) were compared to individuals showing a lower degree of fissurization or a rightward asymmetric folding (REST). Data from two experiments, a masked Stroop paradigm and a combined go/no-go and stop-signal task, are reported. With the masked Stroop task, LEFT subjects revealed a better processing of incongruent Stroop stimuli when compared to REST subjects. This was reflected in both augmented N400 responses as well as significantly higher accuracy scores. In addition, similar effects were found with event-related potentials from the combined go/no-go and stop-signal task. Here, the N200 but not the P300, which have been associated with conflict-related and evaluative processing stages, respectively, was found to be significantly increased with LEFT subjects. The results of this study foster an association of midcingulate fissurization with differences in behavior and neurophysiological functioning related to cognitive control.

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.

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.

Dynamics of auditory plasticity after cochlear implantation: a longitudinal study.

Human representational cortex may fundamentally alter its organization and (re)gain the capacity for auditory processing even when it is deprived of its input for more than two decades. Stimulus-evoked brain activity was recorded in post-lingual deaf patients after implantation of a cochlear prosthesis, which partly restored their hearing. During a 2 year follow-up study this activity revealed almost normal component configuration and was localized in the auditory cortex, demonstrating adequacy of the cochlear implant stimulation. Evoked brain activity increased over several months after the cochlear implant was turned on. This is taken as a measure of the temporal dynamics of plasticity of the human auditory system after implantation of cochlear prosthesis.

Stimulus induced desynchronization of human auditory 40-Hz steady-state responses.

The hypothesis that gamma-band oscillations are related to the representation of an environmental scene in the cerebral cortex after binding of corresponding perceptual elements is currently under discussion. One question is how the sensory system reacts to a fast change in the scene if perceptual elements are rigidly bound together. A reset of the gamma-band oscillation forced by a change in sensory input may dissolve the binding, which then would be re-established for the new sensation. We studied the reset of gamma-band oscillations on the 40-Hz auditory steady-state responses (ASSR) by means of whole-head magnetoencephalography (MEG). The rhythm of 40-Hz AM of a 500-Hz tone evoked the ASSR, and a short noise burst served as a concurrent stimulus. Possible direct interactions of the auditory stimuli were excluded by presenting the noise impulse in a different frequency channel (2,000-3,000 Hz) to the contralateral ear. The concurrent stimulus induced a considerable decrement in the amplitude of ASSR, which was localized in primary auditory cortices. This decrement lasted 250 ms and was significantly longer than the duration of the transient gamma-band response evoked by the noise burst. Thus it could not be explained by any linear superimposition of the responses. The time courses of ASSR amplitude and phase during recovery from the decrement resembled those after stimulus onset, indicating that a new ASSR was built up after the resetting stimulus. The results are discussed as reset of oscillations in human thalamocortical networks.

The dependence of the auditory evoked N1m decrement on the bandwidth of preceding notch-filtered noise.

The auditory evoked response is known to be changed by a preceding sound. In this study we investigated by means of magnetoencephalography how a preceding notch-filtered noise (NFN) with different bandwidths influences the human auditory evoked response elicited by the following test stimulus. We prepared white noise (WN) and four NFNs which were derived from WN by suppressing frequency regions around 1 kHz with 1/8-, 1/4-, 1/2- and 1-octave bandwidths. Stimulation for 3 s with this set of noises resulted in differences in responsiveness to a 1-kHz test tone presented 500 ms after the offset of the noises. The N1m response to the 1-kHz test tone stimulus was at a minimum when the preceding NFN had 1/4-octave stop-band frequencies as compared with 1/8-, 1/2- and 1-octave NFN and WN. This N1m decrement is explained by the imbalanced neural activities caused by habituation and lateral inhibition in the auditory system. The results contribute to understanding of the inhibitory system in the human auditory cortex.

Right hemispheric laterality of human 40 Hz auditory steady-state responses.

Hemispheric asymmetries during auditory sensory processing were examined using whole-head magnetoencephalographic recordings of auditory evoked responses to monaurally and binaurally presented amplitude-modulated sounds. Laterality indices were calculated for the transient onset responses (P1m and N1m), the transient gamma-band response, the sustained field (SF) and the 40 Hz auditory steady-state response (ASSR). All response components showed laterality toward the hemisphere contralateral to the stimulated ear. In addition, the SF and ASSR showed right hemispheric (RH) dominance. Thus, laterality of sustained response components (SF and ASSR) was distinct from that of transient responses. ASSR and SF are sensitive to stimulus periodicity. Consequently, ASSR and SF likely reflect periodic stimulus attributes and might be relevant for pitch processing based on temporal stimulus regularities. In summary, the results of the present studies demonstrate that asymmetric organization in the cerebral auditory cortex is already established on the level of sensory processing.

Lateral inhibition and habituation of the human auditory cortex.

The goal of this study was to compare the lateral inhibition and the habituation in the human auditory cortex, two important physiological effects during auditory processing that can be reliably measured by means of magnetoencephalography when recording auditory evoked fields. Applying 40-Hz amplitude-modulated stimuli allowed us to record simultaneously the slow transient evoked and the steady-state fields and thus to characterize the lateral inhibition and the habituation effect in primary and non-primary auditory cortical structures. The main finding of the study is that the lateral inhibition effect of non-primary auditory areas as measured on the major component of the slow transient auditory evoked field (N1) is significantly stronger than the corresponding habituation effect. By contrast, this effect was not observed for the 40-Hz steady-state fields, characterizing the activation of the primary auditory cortex in humans. The results might be interpreted as (i) evidence that the inhibition mediated by lateral connections is stronger than the habituation of excitatory neurons in the non-primary auditory cortex and (ii) the processing hierarchy in the human auditory cortex is demonstrated by the different behaviour of lateral inhibition and habituation in primary and non-primary auditory cortical structures.

The effect of attention on the auditory steady-state response.

40-Hz auditory steady state responses to amplitude modulated tones were recorded with magnetoencephalography to investigate the effect of focused attention. A modulation discrimination task and a destructive visual task established the attended and the non-attended experimental conditions. A strong contrast between these conditions was demonstrated by largely enhanced sustained responses under the attention condition. A significant attentional effect on the ASSR amplitude was observed mostly in the left hemisphere between 200 to 500 ms after stimulus onset. In contrast, transient gamma-band and N1 responses were not affected by the different states of attention.

Stimulus induced reset of 40-Hz auditory steady-state responses.

Auditory steady-state responses (ASSR) were evoked with 40-Hz amplitude modulated 500-Hz tones. An additional impulse-like noise stimulus (2,000 +/- 500 Hz) with spectrum clearly distinct from the one of the AM sound, induced pronounced perturbations in the ASSR. The effect of the interfering noise was interpreted as (1) reset of the ASSR because of a sudden loss in phase coherence, (2) a decrease in signal power immediately after presentation of the noise impulse, and (3) a modulation of ASSR amplitude and phase resembling the time course of the ASSR onset. The time-course of the ASSR onset was interpreted as reflecting temporal integration over several 100 ms. The reset of the ASSR was discussed as a powerful mechanism, which allows for fast reaction to a short stimulus change that overcomes the disadvantage of the ASSR's long integration time constant.

MEG analysis of "theory of mind" in emotional vignettes comprehension.

OBJECTIVE: Several studies suggested that an impaired "theory of mind" might play a key role in psychiatric disorders, such as autism and schizophrenia. Medial frontal lobe lesions of the right frontal lobe were reported to impair this ability. The aim of our study was to locate areas of the brain associated with the process of "theory of mind" in normal subjects. METHODS: In order to index the activity of brain areas related to "theory of mind" reasoning in sixteen normal adults, we administered an emotional ("happy", "sad", "angry" and "neutral") vignettes comprehension task during magnetoencephalography (MEG) recordings and analyzed these data by using SAM (synthetic aperture magnetometry), SPM99 and the permutation method. Subjects were presented with eight different videotaped social situations (each emotion has two vignettes) and were asked to indicate which emotion they represented. RESULTS: Statistically significant activation in the comparison of "happy"-"sad" and "angry"-"sad" was observed in the bilateral medial prefrontal cortices in the alpha frequency band. There were no significant differences in comparisons of each type of emotional vignette to the neutral vignettes, "happy"-"angry" comparison, and male-female comparisons. There was no significant difference in other frequency bands. CONCLUSION: This result suggests that bilateral medial prefrontal cortex are involved in the comprehension of emotional states of others.

Cortical oscillations modulated by congruent and incongruent audiovisual stimuli.

Congruent or incongruent grapheme-phoneme stimuli are easily perceived as one or two linguistic objects. The main objective of this study was to investigate the changes in cortical oscillations that reflect the processing of congruent and incongruent audiovisual stimuli. Graphemes were Japanese Hiragana characters for four different vowels (/a/, /o/, /u/, and /i/). They were presented simultaneously with their corresponding phonemes (congruent) or non-corresponding phonemes (incongruent) to native-speaking Japanese participants. Participants' reaction times to the congruent audiovisual stimuli were significantly faster by 57 ms as compared to reaction times to incongruent stimuli. We recorded the brain responses for each condition using a whole-head magnetoencephalograph (MEG). A novel approach to analysing MEG data, called synthetic aperture magnetometry (SAM), was used to identify event-related changes in cortical oscillations involved in audiovisual processing. The SAM contrast between congruent and incongruent responses revealed greater event-related desynchonization (8-16 Hz) bilaterally in the occipital lobes and greater event-related synchronization (4-8 Hz) in the left transverse temporal gyrus. Results from this study further support the concept of interactions between the auditory and visual sensory cortices in multi-sensory processing of audiovisual objects.