Assessing brain neuroplasticity: Surface morphometric analysis of cortical changes induced by Quadrato motor training.

Morphological markers for brain plasticity are still lacking and their findings are challenged by the extreme variability of cortical brain surface. Trying to overcome the "correspondence problem," we applied a landmark-free method (the generalized procrustes surface analysis (GPSA)) for investigating the shape variation of cortical surface in a group of 40 healthy volunteers (i.e., the practice group) subjected to daily motor training known as Quadrato motor training (QMT). QMT is a sensorimotor walking meditation that aims at balancing body, cognition, and emotion. More specifically, QMT requires coordination and attention and consists of moving in one of three possible directions on corners of a 50 × 50 cm2. Brain magnetic resonance images (MRIs) of practice group (acquired at baseline, as well as after 6 and 12 weeks of QMT), were 3D reconstructed and here compared with brain MRIs of six more volunteers never practicing the QMT (naïve group). Cortical regions mostly affected by morphological variations were visualized on a 3D average color-scaled brain surface indicating from higher (red) to lower (blue) levels of variation. Cortical regions interested in most of the shape variations were as follows: (1) the supplementary motor cortex; (2) the inferior frontal gyrus (pars opercolaris) and the anterior insula; (3) the visual cortex; (4) the inferior parietal lobule (supramarginal gyrus and angular gyrus). Our results show that surface morphometric analysis (i.e., GPSA) can be applied to assess brain neuroplasticity processes, such as those stimulated by QMT.

Inward versus reward: white matter pathways in extraversion.

The trait of extraversion is one of the longest-standing domains that captures the social dimension of personality and can potentially explain the covariation of a wide variety of behaviors. To date, there is a growing recognition that human behavior should be specified not only through the psychological mechanisms underlying each trait but also through their underlying neurobehavioral systems. While imaging studies have revealed important initial insights into the structural and functional neural correlates of extraversion, current knowledge about the relationships between extraversion and brain structures is still rather limited, especially with regard to the relationship between extraversion and white matter (WM). In this study, we aimed to investigate WM microstructure in extraversion in greater depth. Thirty-five healthy volunteers (21 women; mean age 35) underwent magnetic resonance imaging, as a part of a larger project aimed at investigating the longitudinal effect of motor training. WM integrity was assessed using the diffusion tensor imaging technique combining multiple diffusion tensor measures. Extraversion was assessed by the Eysenck Personality Questionnaire-Revised. Voxelwise correlation analyses between fractional anisotropy, axial diffusivities, and radial diffusivities maps and extraversion score showed decreased connectivity in the right inferior fronto-occipital fasciculus and forceps major among individuals who had high extraversion ratings. In conclusion, individual differences in extraversion may reflect differential organization of the WM tracts connecting frontal cortex, temporal, and occipital areas, which are related to socioemotional and control functions.

Personalizing the Electrode to Neuromodulate an Extended Cortical Region.

BACKGROUND: Among transcranial electric stimulation (tES) parameters, personalizing the electrode geometry might help overcome the individual variability of the induced effects. OBJECTIVE/HYPOTHESIS: To test the need for electrode personalization, instead of a universal electrode for everyone, to induce neuromodulation effects on the bilateral primary motor cortex (M1) devoted to upper and lower limb representation. METHODS: By an ad-hoc neuronavigation procedure, we shaped the personalized electrode and positioned it matching the projection on the scalp of the individual central sulcus by a 2 cm strip, with total area of 35 cm(2). The non-personalized electrode, i.e., equal for all subjects, was a 2 cm wide strip size-matched with the personalized electrode but shaped on a standard model fitting the curve passing through C3-CZ-C4 sites of the electroencephalographic (EEG) 10-20 International System. To test neuromodulation electrode-dependent efficacy, we induced a 20 Hz sinusoidal modulated current (transcranial alternating current stimulation, tACS) because it produces online effects. We simultaneously collected left and right hand and leg motor potentials (MEP) that were evoked by a rounded transcranial magnetic stimulation (TMS) coil. Through each electrode we delivered both real and sham stimulations. RESULTS: While cortical excitability during tACS increased during both the non-personalized and the personalized electrodes for the leg, the hand representation excitability enhancement was induced selectively when using the personalized electrode. The results were consistent bilaterally. CONCLUSIONS: We documented that by using a personalized electrode it is possible to induce the neuromodulation of a predetermined extended cortical target, which did not occur with a non-personalized electrode. Our findings can help in building neuromodulation methods that might compensate for individual alterations across specific brain networks.

Regional personalized electrodes to select transcranial current stimulation target.

RATIONALE: Personalizing transcranial stimulations promises to enhance beneficial effects for individual patients. OBJECTIVE: To stimulate specific cortical regions by developing a procedure to bend and position custom shaped electrodes; to probe the effects on cortical excitability produced when the properly customized electrode is targeting different cortical areas. METHOD: An ad hoc neuronavigation procedure was developed to accurately shape and place the personalized electrodes on the basis of individual brain magnetic resonance images (MRI) on bilateral primary motor (M1) and somatosensory (S1) cortices. The transcranial alternating current stimulation (tACS) protocol published by Feurra et al. (2011b) was used to test the effects on cortical excitability of the personalized electrode when targeting S1 or M1. RESULTS: Neuronal excitability as evaluated by tACS was different when targeting M1 or S1, with the General Estimating Equation model indicating a clear tCS Effect (p < 0.001), and post hoc comparisons showing solely M1 20 Hz tACS to reduce M1 excitability with respect to baseline and other tACS conditions. CONCLUSIONS: The present work indicates that specific cortical regions can be targeted by tCS properly shaping and positioning the stimulating electrode. SIGNIFICANCE: Through multimodal brain investigations continuous efforts in understanding the neuronal changes related to specific neurological or psychiatric diseases become more relevant as our ability to build the compensating interventions improves. An important step forward on this path is the ability to target the specific cortical area of interest, as shown in the present pilot work.

Is HCMV vaccine an unmet need? The state of art of vaccine development.

Congenital HCMV infection is the most frequent congenital infection, with an incidence of 0.2- 2.5 percent among all live births. About 11 percent of infected newborns show symptoms at birth, including hepato-splenomegaly, thrombocytopenia, neurologic involvement, hearing impairment and visual deficit. Moreover, 5-25 percent of the asymptomatic congenital HCMV-infected neonates will develop sequelae over months or even years. The relevant social burden, the economic costs of pre-natal screening, post-natal diagnosis, follow-up and possible therapy, although still limited, are the major factors to be considered. Several types of vaccines have been explored in order to develop an effective and safe HCMV vaccine: live attenuated, subunit, vectored, peptide, DNA, and subviral ones, but none are available for use. This review illustrates the different vaccine types studied to date, focusing on the possible vaccination strategy to be implemented once the HCMV vaccine is available, in terms of target population.

Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia.

OBJECTIVE: To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). METHOD: Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. RESULTS: Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. CONCLUSION: These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome.

Sequential combined treatment with intravitreal bevacizumab and photodynamic therapy for retinal angiomatous proliferation.

PURPOSE: To study visual and anatomical outcomes of sequenced combined therapy using intravitreal bevacizumab followed by photodynamic therapy (PDT) in eyes with retinal angiomatous proliferation (RAP). Safety and rate of intravitreal injections were also evaluated. METHODS: We conducted a prospective non-comparative pilot study of consecutive patients newly diagnosed with RAP. PDT guided by indocyanine green (ICG) angiography was applied 8+/-2 days after the intravitreal bevacizumab (1.25 mg) injection. At baseline and every month after the injection, best-corrected visual acuity (BCVA) measurement, complete eye examination including dynamic fluorescein and ICG angiography, and optical coherence tomography (OCT) were performed. RESULTS: In all, 21 eyes of 18 patients with RAP were enrolled. The mean age was 77 (range 65-86) years. Mean visual acuity at baseline was 0.63+/-0.25 logMAR. After treatment BCVA showed no statistically significant differences between each visit (P=0.10, ANOVA). At 9 months, the BCVA improved by three or more lines in three eyes (14%), remained stable in twelve eyes (57%), and worsened in six eyes (29%). Foveal thickness decreased significantly between baseline and all the follow-up visits (P<0.01, ANOVA). A total of 36 intravitreal injections were given during the study with a mean of 1.7 injections per eye (range 1-3 injections per eye). No ocular or systemic adverse events were reported. CONCLUSION: A possible synergistic effect may arise from the combination of intravitreal bevacizumab with PDT for the treatment of RAP. These findings also suggest a possible benefit of combo therapy in the rate of intravitreal re-injections.

Gait analysis and cerebral volumes in Down's syndrome.

The aim of this study was to look for a relationship between cerebral volumes computed using a voxel-based morphometry algorithm and walking patterns in individuals with Down's syndrome (DS), in order to investigate the origin of the motor problems in these subjects with a view to developing appropriate rehabilitation programmes. Nine children with DS underwent a gait analysis (GA) protocol that used a 3D motion analysis system, force plates and a video system, and magnetic resonance imaging (MRI). Analysis of GA graphs allowed a series of parameters to be defined and computed in order to quantify gait patterns. By combining some of the parameters it was possible to obtain a 3D description of gait in terms of distance from normal values. Finally, the results of cerebral volume analysis were compared with the gait patterns found. A strong relationship emerged between cerebellar vermis volume reduction and quality of gait and also between grey matter volume reduction of some cerebral areas and asymmetrical gait. An evaluation of high-level motor deficits, reflected in a lack or partial lack of proximal functions, is important in order to define a correct rehabilitation programme.

Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels.

CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect on HCV-specific CD4+ T cell reactivity by flow cytometry for intracellular cytokine production and proliferation assay. HCV-specific CD4+CD25(+high) T cells consistently produced transforming growth factor (TGF)-beta but only limited amounts of interleukin (IL)-10 and no IL-2 and interferon (IFN)-gamma. The HCV-specific TGF-beta response by CD4+CD25(+high) T cells was significantly greater in patients with normal ALT compared to patients with elevated ALT. In addition, a significant inverse correlation was found between the HCV-specific TGF-beta response by CD4+CD25(+high) T cells and liver inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen-induced IFN-gamma production and proliferation of CD4+ T cells were greater in patients with elevated ALT compared with patients with normal ALT. Depletion of CD4+CD25+ cells from PBMC resulted in an increase of both IFN-gamma production and proliferation of HCV-specific CD4+ T cells that was significantly greater in patients with normal ALT levels compared with patients with elevated ALT. In addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be significantly more potent to suppress CD4+ T cell reactivity with respect to those from patients with elevated ALT. In conclusion, these data support the hypothesis that CD4+CD25+ cells may play a role in controlling chronic inflammatory response and hepatic damage in chronic HCV carriers.

Assessing cortical functional connectivity by linear inverse estimation and directed transfer function: simulations and application to real data.

OBJECTIVE: To test a technique called Directed Transfer Function (DTF) for the estimation of human cortical connectivity, by means of simulation study and human study, using high resolution EEG recordings related to finger movements. METHODS: The method of the Directed Transfer Function (DTF) is a frequency-domain approach, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. Since the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites, we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. The simulation study was followed by an analysis of variance (ANOVA) of the results obtained for different levels of Signal to Noise Ratio (SNR) and temporal length, as they have been systematically imposed on simulated signals. The whole methodology was then applied to high resolution EEG data recorded during a visually paced finger movement. RESULTS: The statistical analysis performed returns that during simulations, DTF is able to estimate correctly the imposed connectivity patterns under reasonable operative conditions, i.e. when data exhibit a SNR of at least 3 and a length of at least 75 s of non-consecutive recordings at 64 Hz of sampling rate, equivalent, more generally, to 4800 data samples. CONCLUSIONS: Functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high resolution EEG techniques, linear inverse estimation and the DTF method. SIGNIFICANCE: The estimation of cortical connectivity can be performed not only with hemodynamic measurements, by using functional MRI recordings, but also with modern EEG recordings treated with advanced computational techniques.

Estimation of the cortical functional connectivity with the multimodal integration of high-resolution EEG and fMRI data by directed transfer function.

Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger movements were analyzed with the use of separate EEG or fMRI measurements.

Independent component analysis compared to Laplacian filtering as "deblurring" techniques for event related desynchronization/synchronization.

OBJECTIVES: The aim of the work was to compare two different approaches - one model-dependent, the other data-dependent - for "deblurring" EEG data, in order to improve the estimation of Event-Related Desynchronization/Synchronization. METHODS: Realistic Surface Laplacian filtering (SL) and Infomax Independent Component Analysis (ICA) were applied on multivariate scalp EEG signals (SL: 128 electrodes with MRI-based realistic modeling; ICA: a subset of 19 electrodes, no MRI) prior to beta Event Related Synchronization (ERS) estimation after finger movement in 8 normal subjects. ERS estimation was performed using standard band-pass filtering. ERS peak amplitudes and latencies in the most responsive channel were calculated and the effect of the two methods above was evaluated by one-way analysis of variance (ANOVA) and Sheffe's test. RESULTS: Both methods and their combination significantly improved ERS estimation (greater ERS peak amplitude, p <0.05). The results obtained after ICA on 19 electrodes were not significantly different than the ones obtained with Realistic SL using 128 electrodes and MRI for scalp modeling (p >0.89). CONCLUSIONS: The "low cost" of ICA (19 electrodes, no MRI) imposes such method as a valid alternative to SL filtering. The employ of ICA after SL filtering suggests that the "ideal EEG deblurring method" would unify the two approaches, depending on both the scalp model and the data.

EEG deblurring techniques in a clinical context.

OBJECTIVES: EEG scalp potential distributions recorded in humans are affected by low spatial resolution and by the dependence on the electrical reference used. High resolution EEG technologies are available to drastically increase the spatial resolution of the raw EEG. Such technologies include the computation of surface Laplacian (SL) of the recorded potentials, as well as the use of realistic head models to estimate the cortical sources via linear inverse procedure (low resolution brain electromagnetic tomography, LORETA). However, these deblurring procedures are generally used in conjunction with EEG recordings with 64-128 scalp electrodes and with realistic head models obtained via sequential magnetic resonance images (MRIs) of the subjects. Such recording setup it is not often available in the clinical context, due to both the unavailability of these technologies and the scarce compliance of the patients with them. In this study we addressed the use of SL and LORETA deblurring techniques to analyze data from a standard 10-20 system (19 electrodes) in a group of Alzheimer disease (AD) patients. METHODS: EEG data related to unilateral finger movements were gathered from 10 patients affected by AD. SL and LORETA techniques were applied for source estimation of EEG data. The use of MRIs for the construction of head models was avoided by using the quasi-realistic head model of the Brain Imaging Neurology Institute of Montreal. RESULTS: A similar cortical activity estimated by the SL and LORETA techniques was observed during an identical time period of the acquired EEG data in the examined population. CONCLUSIONS: The results of the present study suggest that both SL and LORETA approaches can be usefully applied in the clinical context, by using quasi-realistic head modeling and a standard 10-20 system as electrode montage (19 electrodes). These results represent a reciprocal cross-validation of the two mathematically independent techniques in a clinical environment.

Coupling between "hand" primary sensorimotor cortex and lower limb muscles after ulnar nerve surgical transfer in paraplegia.

Previous neuroimaging evidence revealed an "invasion" of "hand" over "lower limb" primary sensorimotor cortex in paraplegic subjects, with the exception of a rare patient who received a surgical motor reinnervation of hip-thigh muscles by the ulnar nerve. Here, the authors show that a functional reorganization of cortico-muscular and cortico-cortical oscillatory coupling was related to the recovery of the rare patient, as a paradigmatic case of long-term plasticity in human sensorimotor cortex after motor reinnervation of paraplegic muscles. This conclusion was based on electroencephalographic and electromyographic data collected while the patient and normal control subjects performed isometric muscle contraction of the left hand or lower limb. Cortico-muscular and cortico-cortical coupling was estimated by electroencephalographic-electromyographic coherence and directed transfer function of a multivariate autoregressive model.

Solving the neuroimaging puzzle: the multimodal integration of neuroelectromagnetic and functional magnetic resonance recordings.

In this chapter, advanced methods for the modeling of human cortical activity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are reviewed. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from magnetic resonance images, multidipole source model, and regularized linear inverse source estimates. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) and event-related (coupling of activated voxels) fMRI. As an example, these methods were applied to EEG (128 electrodes) and fMRI data, which were recorded in separate sessions while normal subjects executed voluntary right one-digit movements.

Time-varying cortical connectivity by high resolution EEG and directed transfer function: simulations and application to finger tapping data.

The problem of the definition and evaluation of brain connectivity has become a central one in neuroscience during the latest years, as a way to understand the organization and interaction of cortical areas during the execution of cognitive or motor tasks. The method of the directed transfer function (DTF) is a frequency-domain approach to this problem, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. So far, all the connectivity estimations performed on cerebral electromagnetic signals were computed between signals gathered from the electric or magnetic sensors. However, the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites. In this paper we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. As main contributions of this work, we present the results of a wide simulation study, aiming to evaluate performances of DTF application on this kind of data, and a statistical analysis (via the ANOVA, analysis of variance) of the results obtained for different levels of signal to noise ratio and temporal length, as they have been systematically imposed on simulated signals. Finally, we provide an application to the estimation of cortical connectivity from high resolution EEG recordings related to finger tapping movements.

Multimodal integration of high-resolution EEG and functional magnetic resonance imaging data: a simulation study.

Previous simulation studies have stressed the importance of the use of fMRI priors in the estimation of cortical current density. However, no systematic variations of signal-to-noise ratio (SNR) and number of electrodes were explicitly taken into account in the estimation process. In this simulation study we considered the utility of including information as estimated from fMRI. This was done by using as the dependent variable both the correlation coefficient and the relative error between the imposed and the estimated waveforms at the level of cortical region of interests (ROI). A realistic head and cortical surface model was used. Factors used in the simulations were the different values of SNR of the scalp-generated data, the different inverse operators used to estimated the cortical source activity, the strengths of the fMRI priors in the fMRI-based inverse operators, and the number of scalp electrodes used in the analysis. Analysis of variance results suggested that all the considered factors significantly afflict the correlation and the relative error between the estimated and the simulated cortical activity. For the ROIs analyzed with simulated fMRI hot spots, it was observed that the best estimation of cortical source currents was performed with the inverse operators that used fMRI information. When the ROIs analyzed do not present fMRI hot spots, both standard (i.e., minimum norm) and fMRI-based inverse operators returned statistically equivalent correlation and relative error values.

Computerized processing of EEG-EOG-EMG artifacts for multi-centric studies in EEG oscillations and event-related potentials.

The aim of this study is to present a package including standard software for the electroencephalographic (EEG), electro-oculographic (EOG) and electromyographic (EMG) preliminary data analysis, which may be suitable to standardize the results of many EEG research centers studies (i.e. multi-centric studies) especially focused on event-related potentials. In particular, our software package includes (semi)automatic procedures for (i) EOG artifact detection and correction, (ii) EMG analysis, (iii) EEG artifact analysis, (iv) optimization of the ratio between artifact-free EEG channels and trials to be rejected. The performances of the software package on EOG-EEG-EMG data related to cognitive-motor tasks were evaluated with respect to the preliminary data analysis performed by two expert electroencephalographists (gold standard). Due to its extreme importance for multi-centric EEG studies, we compared the performances of two representative "regression" methods for the EOG correction in time and frequency domains. The aim was the selection of the most suitable method in the perspective of a multi-centric EEG study. The results showed an acceptable agreement of approximately 95% between the human and software behaviors, for the detection of vertical and horizontal EOG artifacts, the measurement of hand EMG responses for a cognitive-motor paradigm, the detection of involuntary mirror movements, and the detection of EEG artifacts. Furthermore, our results indicated a particular reliability of a 'regression' EOG correction method operating in time domain (i.e. ordinary least squares). These results suggest that such a software package could be used for multi-centric EEG studies.

Cortical source estimate of combined high resolution EEG and fMRI data related to voluntary movements.

OBJECTIVES: In this paper, we employed advanced methods for the modeling of human cortical activity related to voluntary right one-digit movements from combined high-resolution electroencepholography (EEG) and functional magnetic resonance imaging (fMRI). METHODS: Multimodal integration between EEG and fMRI data was performed by using realistic head models, a large number of scalp electrodes (128) and the estimation of current density strengths by linear inverse estimation. RESULTS: Increasing of spatial details of the estimated cortical density distributions has been detected by using the proposed integration method with respect to the estimation using EEG data alone. CONCLUSION: The proposed method of multimodal EEG-fMRI data is useful to increase spatial resolution of movement-related potentials and can also be applied to other kinds of event-related potentials.