Vadim V Nikulin

Publications of Vadim V Nikulin

• Attenuation of long-range temporal correlations in the amplitude dynamics of alpha and beta neuronal oscillations in patients with schizophrenia.

  Authors: Vadim V Nikulin, Erik G Jönsson, Tom Brismar

  NeuroImage. 03/2012; 61(1):162-169.

  Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease.Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. However, given that the coordination of neuronal processes in time represents an essential aspect of practically all cognitive operations, it might be strongly affected in patients with schizophrenia. In the present study we aimed at quantifying long-range temporal correlations (LRTC) in patients (18 with schizophrenia; 3 with schizoaffective disorder) and 28 healthy control subjects matched for age and gender. Ongoing neuronal oscillations were recorded with multi-channel EEG at rest condition. LRTC in the range 5-50s were analyzed with Detrended Fluctuation Analysis. The amplitude of neuronal oscillations in alpha and beta frequency ranges did not differ between patients and control subjects. However, LRTC were strongly attenuated in patients with schizophrenia in both alpha and beta frequency ranges. Moreover, the cross-frequency correlation between LRTC belonging to alpha and beta oscillations was stronger for patients than healthy controls, indicating that similar neurophysiological processes affect neuronal dynamics in both frequency ranges. We believe that the attenuation of LRTC is most likely due to the increased variability in neuronal activity, which was previously hypothesized to underlie an excessive switching between the neuronal states in patients with schizophrenia. Attenuated LRTC might allow for more random associations between neuronal activations, which in turn might relate to the occurrence of thought disorders in schizophrenia.

• Cross-frequency decomposition: A novel technique for studying interactions between neuronal oscillations with different frequencies.

  Authors: Vadim V Nikulin, Guido Nolte, Gabriel Curio

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 01/2012;

  OBJECTIVE: We present a novel method for the extraction of neuronal components showing cross-frequency phase synchronization. METHODS: In general the method can be applied for the detection of phaseOBJECTIVE: We present a novel method for the extraction of neuronal components showing cross-frequency phase synchronization. METHODS: In general the method can be applied for the detection of phase interactions between components with frequencies f1 and f2, where f2≈rf1 and r is some integer. We refer to the method as cross-frequency decomposition (CFD), which consists of the following steps: (a) extraction of f1-oscillations with the spatio-spectral decomposition algorithm (SSD); (b) frequency modification of the f1-oscillations obtained with SSD; and (c) finding f2-oscillations synchronous with f1-oscillations using least-squares estimation. RESULTS: Our simulations showed that CFD was capable of recovering interacting components even when the signal-to-noise ratio was as low as 0.01. An application of CFD to the real EEG data demonstrated that cross-frequency phase synchronization between alpha and beta oscillations can originate from the same or remote neuronal populations. CONCLUSIONS: CFD allows a compact representation of the sets of interacting components. The application of CFD to EEG data allows differentiating cross-frequency synchronization arising due to genuine neurophysiological interactions from interactions occurring due to quasi-sinusoidal waveform of neuronal oscillations. SIGNIFICANCE: CFD is a method capable of extracting cross-frequency coupled neuronal oscillations even in the presence of strong noise.

• Alleviating the Influence of Weak Data Asymmetries on Granger-Causal Analyses.

  Authors: Stefan Haufe, Vadim V. Nikulin, Guido Nolte

  Latent Variable Analysis and Signal Separation - 10th International Conference, LVA/ICA 2012, Tel Aviv, Israel, March 12-15, 2012. Proceedings; 01/2012

• Effect of complete stimulus predictability on P3 and N2 components: an electroencephalographic study.

  Authors: Katherina M B von Carlowitz-Ghori, Friederike U Hohlefeld, Zubeyir Bayraktaroglu, Gabriel Curio, Vadim V Nikulin

  Neuroreport. 06/2011; 22(9):459-63.

  In everyday life one may encounter both unpredictable and self-initiated, hence anticipated, events. Here, we analyzed the effects of self-initiated auditory stimulus presentation on P3 and N2In everyday life one may encounter both unpredictable and self-initiated, hence anticipated, events. Here, we analyzed the effects of self-initiated auditory stimulus presentation on P3 and N2 components in an oddball paradigm. If the stimulus sequence was fully self-determined, both components were attenuated in comparison with computer-controlled representation. In contrast, both components were increased when only the stimulus onset was self-initiated, yet the forthcoming stimulus type was unknown. We hypothesize that predictive forward models offer an unifying explanation for the modulation of both P3 and N2 through: (a) attenuation of neuronal responses to anticipated stimuli contingent on one's own motor action and (b) enhancement of responses in case of incongruity between an anticipated action effect and the actual perceptual consequences.

• Optimal imaging of cortico-muscular coherence through a novel regression technique based on multi-channel EEG and un-rectified EMG.

  Authors: Zubeyir Bayraktaroglu, Katherina von Carlowitz-Ghori, Florian Losch, Guido Nolte, Gabriel Curio, Vadim V Nikulin

  NeuroImage. 05/2011; 57(3):1059-67.

  Cortico-muscular coherence (CMC) reflects interactions between muscular and cortical activities as detected with EMG and EEG recordings, respectively. Most previous studies utilized EMG rectificationCortico-muscular coherence (CMC) reflects interactions between muscular and cortical activities as detected with EMG and EEG recordings, respectively. Most previous studies utilized EMG rectification for CMC calculation. Yet, recent modeling studies predicted that EMG rectification might have disadvantages for CMC evaluation. In addition, previously the effect of rectification on CMC was estimated with single-channel EEG which might be suboptimal for detection of CMC. In order to optimally detect CMC with un-rectified EMG and resolve the issue of EMG rectification for CMC estimation, we introduce a novel method, Regression CMC (R-CMC), which maximizes the coherence between EEG and EMG. The core idea is to use multiple regression where narrowly filtered EEG signals serve as predictors and EMG is the dependent variable. We investigated CMC during isometric contraction of the abductor pollicis brevis muscle. In order to facilitate the comparison with previous studies, we estimated the effect of rectification with frequently used Laplacian filtering and C3/C4 vs. linked earlobes. For all three types of analysis, we detected CMC in the beta frequency range above the contralateral sensorimotor areas. The R-CMC approach was validated with simulations and real data and was found capable of recovering CMC even in case of high levels of background noise. When using single channel data, there were no changes in the strength of CMC estimated with rectified or un-rectified EMG--in agreement with the previous findings. Critically, for both Laplacian and R-CMC analyses EMG rectification resulted in significantly smaller CMC values compared to un-rectified EMG. Thus, the present results provide empirical evidence for the predictions from the earlier modeling studies that rectification of EMG can reduce CMC.

• Covert movements trigger repetition suppression of electroencephalography in sensorimotor cortex.

  Authors: Friederike U Hohlefeld, Vadim V Nikulin, Gabriel Curio

  Neuroreport. 02/2011; 22(3):141-5.

  'Repetition suppression' (RS) denotes the decrease of neural responses to repeated external sensory stimuli. We showed that RS can be also triggered by internal processes alone. When individuals'Repetition suppression' (RS) denotes the decrease of neural responses to repeated external sensory stimuli. We showed that RS can be also triggered by internal processes alone. When individuals perform repetitive covert movements, that is, motor imagery or quasi-movements, both of which are associated with pericentral cortical activity without muscle activations, there was a significant recovery of electroencephalographic oscillations over sensorimotor cortices back to resting baseline level. After 58 s of task performance only 20% of α and 5% of β suppressions remained (overt movements: 34% remaining in α, complete recovery in β). This result suggests that various, possibly all, repeated cerebral activations are associated with RS, presumably reflecting the adaptation to stereotyped activation in neural networks.

• A novel method for reliable and fast extraction of neuronal EEG/MEG oscillations on the basis of spatio-spectral decomposition.

  Authors: Vadim V Nikulin, Guido Nolte, Gabriel Curio

  NeuroImage. 01/2011; 55(4):1528-35.

  Neuronal oscillations have been shown to underlie various cognitive, perceptual and motor functions in the brain. However, studying these oscillations is notoriously difficult with EEG/MEG recordingsNeuronal oscillations have been shown to underlie various cognitive, perceptual and motor functions in the brain. However, studying these oscillations is notoriously difficult with EEG/MEG recordings due to a massive overlap of activity from multiple sources and also due to the strong background noise. Here we present a novel method for the reliable and fast extraction of neuronal oscillations from multi-channel EEG/MEG/LFP recordings. The method is based on a linear decomposition of recordings: it maximizes the signal power at a peak frequency while simultaneously minimizing it at the neighboring, surrounding frequency bins. Such procedure leads to the optimization of signal-to-noise ratio and allows extraction of components with a characteristic "peaky" spectral profile, which is typical for oscillatory processes. We refer to this method as spatio-spectral decomposition (SSD). Our simulations demonstrate that the method allows extraction of oscillatory signals even with a signal-to-noise ratio as low as 1:10. The SSD also outperformed conventional approaches based on independent component analysis. Using real EEG data we also show that SSD allows extraction of neuronal oscillations (e.g., in alpha frequency range) with high signal-to-noise ratio and with the spatial patterns corresponding to central and occipito-parietal sources. Importantly, running time for SSD is only a few milliseconds, which clearly distinguishes it from other extraction techniques usually requiring minutes or even hours of computational time. Due to the high accuracy and speed, we suggest that SSD can be used as a reliable method for the extraction of neuronal oscillations from multi-channel electrophysiological recordings.

• Rapid cortical plasticity underlying novel word learning.

  Authors: Yury Shtyrov, Vadim V Nikulin, Friedemann Pulvermüller

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 12/2010; 30(50):16864-7.

  Humans are unique in developing large lexicons as their communication tool. To achieve this, they are able to learn new words rapidly. However, neural bases of this rapid learning, which may be anHumans are unique in developing large lexicons as their communication tool. To achieve this, they are able to learn new words rapidly. However, neural bases of this rapid learning, which may be an expression of a more general cognitive mechanism, are not yet understood. To address this, we exposed our subjects to familiar words and novel spoken stimuli in a short passive perceptual learning session and compared automatic brain responses to these items throughout the learning exposure. Initially, we found enhanced activity for known words, indexing the ignition of their underlying memory traces. However, just after 14 min of learning exposure, the novel items exhibited a significant increase in response magnitude matching in size with that to real words. This activation increase, as we would like to propose, reflects rapid mapping of new word forms onto neural representations. Similar to familiar words, the neural activity subserving rapid learning of new word forms was generated in the left-perisylvian language cortex, especially anterior superior-temporal areas. This first report of a neural correlate of rapid learning suggests that our brain may effectively form new neuronal circuits online as it gets exposed to novel patterns in the sensory input. Understanding such fast learning is key to the neurobiological explanation of the human language faculty and learning mechanisms in general.

• Event-related desynchronization of sensorimotor EEG rhythms in hemiparetic patients with acute stroke.

  Authors: Magdalena Stępień, Jan Conradi, Gunnar Waterstraat, Friederike U Hohlefeld, Gabriel Curio, Vadim V Nikulin

  Neuroscience letters. 11/2010; 488(1):17-21.

  Previous neuroimaging studies based on neurovascular coupling have shown that stroke affects both, strength and spatial extent of brain activation during upper limb movements. Here, we investigatedPrevious neuroimaging studies based on neurovascular coupling have shown that stroke affects both, strength and spatial extent of brain activation during upper limb movements. Here, we investigated the sub-second amplitude dynamics of a direct neuronal measure, i.e., event-related desynchronization (ERD) of EEG oscillations during finger movements, in patients with acute cortical and subcortical stroke. Acute cortical strokes were found to decrease the ERD of alpha oscillations for the affected pericentral sensorimotor areas compared to a control group. Within the cortical stroke group, the affected hemisphere showed a smaller alpha-ERD compared to the unaffected hemisphere when each was contralateral to the acting hand. Furthermore, when cortical stroke patients moved their paretic hand, the ipsilateral (i.e., contralesional) alpha-ERD was stronger than the contralateral (ipsilesional) ERD. Interestingly, the alpha-ERD amplitude in a hemisphere with a cortical stroke was relatively well preserved for non-paretic hand movements compared to alpha-ERD amplitude for paretic hand movements. This finding provides a new perspective for assessing the rehabilitative potential, which could be utilized through training of the still responsive cortical network, e.g., via enforced use of the paretic hand.

• Visual stimuli evoke rapid activation (120 ms) of sensorimotor cortex for overt but not for covert movements.

  Authors: Friederike U Hohlefeld, Vadim V Nikulin, Gabriel Curio

  Brain research. 10/2010; 1368:185-95.

  Overt and covert movements (e.g., motor imagery) have been frequently demonstrated to engage common neuronal substrates in the motor system. However, it is an open question whether this similarity isOvert and covert movements (e.g., motor imagery) have been frequently demonstrated to engage common neuronal substrates in the motor system. However, it is an open question whether this similarity is also present during early stages of stimulus-processing. We utilized the high temporal resolution of multi-channel electroencephalography (EEG) in order to test whether the prior action intention (overt vs. covert movements) differentially modulates early stimulus-processing stages in the cortical sensorimotor system. The subjects performed overt or covert movements contingent upon an instructive visual stimulus (indicating left or right hand performance). We introduced a novel measure, LRPrect, calculated as Lateralized Readiness Potentials from rectified EEG signals. This measure overcomes a problem related to the EEG signal variability due to polarity differences in the spatial distribution of neuronal sources. The LRPrect showed an activation already at 120 ms after stimulus onset (latN120) focally over sensorimotor cortices contralateral to the upcoming hand movement, yet only for overt but not covert movements. Thus the prior action intention differentially routes early stimulus-processing into the sensorimotor system, which might contribute to significantly different behavioral outcomes, i.e., movement generation or inhibition. The present results have implications for studies of motor inhibition and action intention.

• Role of neuronal synchrony in the generation of evoked EEG/MEG responses.

  Authors: Bartosz Telenczuk, Vadim V Nikulin, Gabriel Curio

  Journal of neurophysiology. 10/2010; 104(6):3557-67.

  Evoked EEG/MEG responses are a primary real-time measure of perceptual and cognitive activity in the human brain, but their neuronal generator mechanisms are not yet fully understood. Arguments haveEvoked EEG/MEG responses are a primary real-time measure of perceptual and cognitive activity in the human brain, but their neuronal generator mechanisms are not yet fully understood. Arguments have been put forward in favor of either "phase-reset" of ongoing oscillations or "added-energy" models. Instead of advocating for one or the other model, here we show theoretically that the differentiation between these two generation mechanisms might not be possible if based solely on macroscopic EEG/MEG recordings. Using mathematical modeling, we show that a simultaneous phase reset of multiple oscillating neuronal (microscopic) sources contributing to EEG/MEG can produce evoked responses in agreement with both, the "added-energy" and the "phase-reset" model. We observe a smooth transition between the two models by just varying the strength of synchronization between the multiple microscopic sources. Consequently, because precise knowledge about the strength of microscopic ensemble synchronization is commonly not available in noninvasive EEG/MEG studies, they cannot, in principle, differentiate between the two mechanisms for macroscopic-evoked responses.

• Non-zero mean of oscillations as a mechanism for the generation of evoked responses Reply to "Amplitude asymmetry as a mechanism for the generation of slow evoked responses"

  Authors: Vadim V Nikulin, Klaus Linkenkaer-Hansen, Guido Nolte, Matias J Palva, Gabriel Curio

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 04/2010;

• Miniaturized electroencephalographic scalp electrode for optimal wearing comfort.

  Authors: Vadim V Nikulin, Jewgeni Kegeles, Gabriel Curio

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 03/2010; 121(7):1007-14.

  Current mainstream EEG electrode setups permit efficient recordings, but are often bulky and uncomfortable for subjects. Here we introduce a novel type of EEG electrode, which is designed for anCurrent mainstream EEG electrode setups permit efficient recordings, but are often bulky and uncomfortable for subjects. Here we introduce a novel type of EEG electrode, which is designed for an optimal wearing comfort. The electrode is referred to as C-electrode where "C" stands for comfort. The C-electrode does not require any holder/cap for fixation on the head nor does it use traditional pads/lining of disposable electrodes - thus, it does not disturb subjects. Fixation of the C-electrode on the scalp is based entirely on the adhesive interaction between the very light C-electrode/wire construction (<35 mg) and a droplet of EEG paste/gel. Moreover, because of its miniaturization, both C-electrode (diameter 2-3mm) and a wire (diameter approximately 50 microm) are minimally (or not at all) visible to an external observer. EEG recordings with standard and C-electrodes were performed during rest condition, self-paced movements and median nerve stimulation. The quality of EEG recordings for all three types of experimental conditions was similar for standard and C-electrodes, i.e., for near-DC recordings (Bereitschaftspotential), standard rest EEG spectra (1-45 Hz) and very fast oscillations approximately 600 Hz (somatosensory evoked potentials). The tests showed also that once being placed on a subject's head, C-electrodes can be used for 9h without any loss in EEG recording quality. Furthermore, we showed that C-electrodes can be effectively utilized for Brain-Computer Interfacing. C-electrodes proved to posses a high stability of mechanical fixation (stayed attached with 2.5 g accelerations). Subjects also reported not having any tactile sensations associated with wearing of C-electrodes. C-electrodes provide optimal wearing comfort without any loss in the quality of EEG recordings. We anticipate that C-electrodes can be used in a wide range of clinical, research and emerging neuro-technological environments.

• Non-zero mean and asymmetry of neuronal oscillations have different implications for evoked responses.

  Authors: Vadim V Nikulin, Klaus Linkenkaer-Hansen, Guido Nolte, Gabriel Curio

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 11/2009;

  OBJECTIVE: The aim of the present study was to show analytically and with simulations that it is the non-zero mean of neuronal oscillations, and not an amplitude asymmetry of peaks and troughs, thatOBJECTIVE: The aim of the present study was to show analytically and with simulations that it is the non-zero mean of neuronal oscillations, and not an amplitude asymmetry of peaks and troughs, that is a prerequisite for the generation of evoked responses through a mechanism of amplitude modulation of oscillations. Secondly, we detail the rationale and implementation of the "baseline-shift index" (BSI) for deducing whether empirical oscillations have non-zero mean. Finally, we illustrate with empirical data why the "amplitude fluctuation asymmetry" (AFA) index should be used with caution in research aimed at explaining variability in evoked responses through a mechanism of amplitude modulation of ongoing oscillations. METHODS: An analytical approach, simulations and empirical MEG data were used to compare the specificity of BSI and AFA index to differentiate between a non-zero mean and a non-sinusoidal shape of neuronal oscillations. RESULTS: Both the BSI and the AFA index were sensitive to the presence of non-zero mean in neuronal oscillations. The AFA index, however, was also sensitive to the shape of oscillations even when they had a zero mean. CONCLUSIONS: Our findings indicate that it is the non-zero mean of neuronal oscillations, and not an amplitude asymmetry of peaks and troughs, that is a prerequisite for the generation of evoked responses through a mechanism of amplitude modulation of oscillations. SIGNIFICANCE: A clear distinction should be made between the shape and non-zero mean properties of neuronal oscillations. This is because only the latter contributes to evoked responses, whereas the former does not.

• Estimating vector fields using sparse basis field expansions

  Authors: Stefan Haufe, Vadim V. Nikulin, Andreas Ziehe, Klaus-Robert Müller, Guido Nolte

  01/2009: pages 617--624;

• Robustly estimating the flow direction of information in complex physical systems.

  Authors: Guido Nolte, Andreas Ziehe, Vadim V Nikulin, Alois Schlögl, Nicole Krämer, Tom Brismar, Klaus-Robert Müller

  Physical review letters. 06/2008; 100(23):234101.

  We propose a new measure (phase-slope index) to estimate the direction of information flux in multivariate time series. This measure (a) is insensitive to mixtures of independent sources, (b) givesWe propose a new measure (phase-slope index) to estimate the direction of information flux in multivariate time series. This measure (a) is insensitive to mixtures of independent sources, (b) gives meaningful results even if the phase spectrum is not linear, and (c) properly weights contributions from different frequencies. These properties are shown in extended simulations and contrasted to Granger causality which yields highly significant false detections for mixtures of independent sources. An application to electroencephalography data (eyes-closed condition) reveals a clear front-to-back information flow.

• Combining sparsity and rotational invariance in EEG/MEG source reconstruction.

  Authors: Stefan Haufe, Vadim V Nikulin, Andreas Ziehe, Klaus-Robert Müller, Guido Nolte

  NeuroImage. 06/2008;

  We introduce Focal Vector Field Reconstruction (FVR), a novel technique for the inverse imaging of vector fields. The method was designed to simultaneously achieve two goals: a) invariance withWe introduce Focal Vector Field Reconstruction (FVR), a novel technique for the inverse imaging of vector fields. The method was designed to simultaneously achieve two goals: a) invariance with respect to the orientation of the coordinate system, and b) a preference for sparsity of the solutions and their spatial derivatives. This was achieved by defining the regulating penalty function, which renders the solutions unique, as a global l(1)-norm of local l(2)-norms. We show that the method can be successfully used for solving the EEG inverse problem. In the joint localization of 2-3 simulated dipoles, FVR always reliably recovers the true sources. The competing methods have limitations in distinguishing close sources because their estimates are either too smooth (LORETA, Minimum l(1)-norm) or too scattered (Minimum l(2)-norm). In both noiseless and noisy simulations, FVR has the smallest localization error according to the Earth Mover's Distance (EMD), which is introduced here as a meaningful measure to compare arbitrary source distributions. We also apply the method to the simultaneous localization of left and right somatosensory N20 generators from real EEG recordings. Compared to its peers FVR was the only method that delivered correct location of the source in the somatosensory area of each hemisphere in accordance with neurophysiological prior knowledge.

• Quasi-movements: a novel motor-cognitive phenomenon.

  Authors: Vadim V Nikulin, Friederike U Hohlefeld, Arthur M Jacobs, Gabriel Curio

  Neuropsychologia. 02/2008; 46(2):727-42.

  We introduce quasi-movements and define them as volitional movements which are minimized by the subject to such an extent that finally they become undetectable by objective measures. They areWe introduce quasi-movements and define them as volitional movements which are minimized by the subject to such an extent that finally they become undetectable by objective measures. They are intended as overt movements, but the absence of the measurable motor responses and the subjective experience make quasi-movements similar to motor imagery. We used the amplitude dynamics of electroencephalographic alpha oscillations as a marker of the regional involvement of cortical areas in three experimental tasks: movement execution, kinesthetic motor imagery, and quasi-movements. All three conditions were associated with a significant suppression of alpha oscillations over the sensorimotor hand area of the contralateral hemisphere. This suppression was strongest for executed movements, and stronger for quasi-movements than for motor imagery. The topography of alpha suppression was similar in all three conditions. Proprioceptive sensations related to quasi-movements contribute to the assumption that the "sense of movement" can originate from central efferent processes. Quasi-movements are also congruent with the postulated continuity between motor imagery and movement preparation/execution. We also show that in healthy subjects quasi-movements can be effectively used in brain-computer interface research leading to a significantly smaller classification error ( approximately 47% of relative decrease) in comparison to the errors obtained with conventionally used motor imagery strategies.

• Robustly estimating the flow direction of information in complex physical systems

  Authors: Guido Nolte, Andreas Ziehe, Vadim V Nikulin, Alois Schlögl, Nicole Krämer, Tom Brismar, Klaus-Robert Müller

  12/2007;

  We propose a new measure to estimate the direction of information flux in multivariate time series from complex systems. This measure, based on the slope of the phase spectrum (Phase Slope Index) hasWe propose a new measure to estimate the direction of information flux in multivariate time series from complex systems. This measure, based on the slope of the phase spectrum (Phase Slope Index) has invariance properties that are important for applications in real physical or biological systems: (a) it is strictly insensitive to mixtures of arbitrary independent sources, (b) it gives meaningful results even if the phase spectrum is not linear, and (c) it properly weights contributions from different frequencies. Simulations of a class of coupled multivariate random data show that for truly unidirectional information flow without additional noise contamination our measure detects the correct direction as good as the standard Granger causality. For random mixtures of independent sources Granger Causality erroneously yields highly significant results whereas our measure correctly becomes non-significant. An application of our novel method to EEG data (88 subjects in eyes-closed condition) reveals a strikingly clear front-to-back information flow in the vast majority of subjects and thus contributes to a better understanding of information processing in the brain. Comment: 5 pages, 4 figures

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• Effects of NMDA receptor antagonist memantine on mismatch negativity.

  Authors: Milena Korostenskaja, Vadim V Nikulin, Dubravko Kicić, Anna V Nikulina, Seppo Kähkönen

  Brain research bulletin. 06/2007; 72(4-6):275-83.

  Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease andMismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease and schizophrenia, indicating deficits in involuntary attention. N-Methyl-D-aspartate (NMDA) receptor-mediated glutamate dysfunction is suggested to underlie these deficits. However, the role of NMDA receptors in involuntary attention is poorly understood. Memantine is an NMDA receptor antagonist that has been demonstrated to be effective in the treatment of patients with Alzheimer's disease. We aimed to investigate whether a single dose of memantine would affect MMN/MMNm in healthy subjects studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Monaural left-ear auditory stimuli were presented in a passive oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded in 13 healthy subjects after oral administration of 30mg of memantine or placebo in a randomized, double-blind, cross-over design. MMNm was analyzed using equivalent current dipoles. MMN was evaluated from frontocentral electrodes. Memantine lowered subjects' arousal level as measured by visual analog scales, and enhanced the amplitude of MMN in EEG. No differences in MMN latency were observed in MEG or EEG. Memantine did not affect the location, strength, amplitude or latency of MMNm, P1m, and N1m components. No changes in amplitude or latency were observed for P1 and N1 peaks. These results indicate that memantine affects involuntary attention without otherwise changing auditory processing of the stimuli. As memantine-induced changes in MMN were detected only in EEG, we suggest that the effect is mostly related to the frontal cortex.