Combined MEG and EEG show reliable patterns of electromagnetic brain activity during natural viewing.

Naturalistic stimuli such as movies are increasingly used to engage cognitive and emotional processes during fMRI of brain hemodynamic activity. However, movies have been little utilized during magnetoencephalography (MEG) and EEG that directly measure population-level neuronal activity at a millisecond resolution. Here, subjects watched a 17-min segment from the movie Crash (Lionsgate Films, 2004) twice during simultaneous MEG/EEG recordings. Physiological noise components, including ocular and cardiac artifacts, were removed using the DRIFTER algorithm. Dynamic estimates of cortical activity were calculated using MRI-informed minimum-norm estimation. To improve the signal-to-noise ratio (SNR), principal component analyses (PCA) were employed to extract the prevailing temporal characteristics within each anatomical parcel of the Freesurfer Desikan-Killiany cortical atlas. A variety of alternative inter-subject correlation (ISC) approaches were then utilized to investigate the reliability of inter-subject synchronization during natural viewing. In the first analysis, the ISCs of the time series of each anatomical region over the full time period across all subject pairs were calculated and averaged. In the second analysis, dynamic ISC (dISC) analysis, the correlation was calculated over a sliding window of 200 ms with 3.3 ms steps. Finally, in a between-run ISC analysis, the between-run correlation was calculated over the dynamic ISCs of the two different runs after the Fisher z-transformation. Overall, the most reliable activations occurred in occipital/inferior temporal visual and superior temporal auditory cortices as well as in the posterior cingulate, precuneus, pre- and post-central gyri, and right inferior and middle frontal gyri. Significant between-run ISCs were observed in superior temporal auditory cortices and inferior temporal visual cortices. Taken together, our results show that movies can be utilized as naturalistic stimuli in MEG/EEG similarly as in fMRI studies.

Neuronal representations of distance in human auditory cortex.

Neuronal mechanisms of auditory distance perception are poorly understood, largely because contributions of intensity and distance processing are difficult to differentiate. Typically, the received intensity increases when sound sources approach us. However, we can also distinguish between soft-but-nearby and loud-but-distant sounds, indicating that distance processing can also be based on intensity-independent cues. Here, we combined behavioral experiments, fMRI measurements, and computational analyses to identify the neural representation of distance independent of intensity. In a virtual reverberant environment, we simulated sound sources at varying distances (15-100 cm) along the right-side interaural axis. Our acoustic analysis suggested that, of the individual intensity-independent depth cues available for these stimuli, direct-to-reverberant ratio (D/R) is more reliable and robust than interaural level difference (ILD). However, on the basis of our behavioral results, subjects' discrimination performance was more consistent with complex intensity-independent distance representations, combining both available cues, than with representations on the basis of either D/R or ILD individually. fMRI activations to sounds varying in distance (containing all cues, including intensity), compared with activations to sounds varying in intensity only, were significantly increased in the planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation. This fMRI result suggests that neurons in posterior nonprimary auditory cortices, in or near the areas processing other auditory spatial features, are sensitive to intensity-independent sound properties relevant for auditory distance perception.

Lateralized parietotemporal oscillatory phase synchronization during auditory selective attention.

Based on the infamous left-lateralized neglect syndrome, one might hypothesize that the dominating right parietal cortex has a bilateral representation of space, whereas the left parietal cortex represents only the contralateral right hemispace. Whether this principle applies to human auditory attention is not yet fully clear. Here, we explicitly tested the differences in cross-hemispheric functional coupling between the intraparietal sulcus (IPS) and auditory cortex (AC) using combined magnetoencephalography (MEG), EEG, and functional MRI (fMRI). Inter-regional pairwise phase consistency (PPC) was analyzed from data obtained during dichotic auditory selective attention task, where subjects were in 10-s trials cued to attend to sounds presented to one ear and to ignore sounds presented in the opposite ear. Using MEG/EEG/fMRI source modeling, parietotemporal PPC patterns were (a) mapped between all AC locations vs. IPS seeds and (b) analyzed between four anatomically defined AC regions-of-interest (ROI) vs. IPS seeds. Consistent with our hypothesis, stronger cross-hemispheric PPC was observed between the right IPS and left AC for attended right-ear sounds, as compared to PPC between the left IPS and right AC for attended left-ear sounds. In the mapping analyses, these differences emerged at 7-13Hz, i.e., at the theta to alpha frequency bands, and peaked in Heschl's gyrus and lateral posterior non-primary ACs. The ROI analysis revealed similarly lateralized differences also in the beta and lower theta bands. Taken together, our results support the view that the right parietal cortex dominates auditory spatial attention.

Improving the spatial resolution of magnetic resonance inverse imaging via the blipped-CAIPI acquisition scheme.

Using simultaneous acquisition from multiple channels of a radio-frequency (RF) coil array, magnetic resonance inverse imaging (InI) achieves functional MRI acquisitions at a rate of 100ms per whole-brain volume. InI accelerates the scan by leaving out partition encoding steps and reconstructs images by solving under-determined inverse problems using RF coil sensitivity information. Hence, the correlated spatial information available in the coil array causes spatial blurring in the InI reconstruction. Here, we propose a method that employs gradient blips in the partition encoding direction during the acquisition to provide extra spatial encoding in order to better differentiate signals from different partitions. According to our simulations, this blipped-InI (bInI) method can increase the average spatial resolution by 15.1% (1.3mm) across the whole brain and from 32.6% (4.2mm) in subcortical regions, as compared to the InI method. In a visual fMRI experiment, we demonstrate that, compared to InI, the spatial distribution of bInI BOLD response is more consistent with that of a conventional echo-planar imaging (EPI) at the level of individual subjects. With the improved spatial resolution, especially in subcortical regions, bInI can be a useful fMRI tool for obtaining high spatiotemporal information for clinical and cognitive neuroscience studies.

Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise.

How can we concentrate on relevant sounds in noisy environments? A "gain model" suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A "tuning model" suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for "frequency tagging" of attention effects on maskers. Noise masking reduced early (50-150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50-150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.

Dynamic oscillatory processes governing cued orienting and allocation of auditory attention.

In everyday listening situations, we need to constantly switch between alternative sound sources and engage attention according to cues that match our goals and expectations. The exact neuronal bases of these processes are poorly understood. We investigated oscillatory brain networks controlling auditory attention using cortically constrained fMRI-weighted magnetoencephalography/EEG source estimates. During consecutive trials, participants were instructed to shift attention based on a cue, presented in the ear where a target was likely to follow. To promote audiospatial attention effects, the targets were embedded in streams of dichotically presented standard tones. Occasionally, an unexpected novel sound occurred opposite to the cued ear to trigger involuntary orienting. According to our cortical power correlation analyses, increased frontoparietal/temporal 30-100 Hz gamma activity at 200-1400 msec after cued orienting predicted fast and accurate discrimination of subsequent targets. This sustained correlation effect, possibly reflecting voluntary engagement of attention after the initial cue-driven orienting, spread from the TPJ, anterior insula, and inferior frontal cortices to the right FEFs. Engagement of attention to one ear resulted in a significantly stronger increase of 7.5-15 Hz alpha in the ipsilateral than contralateral parieto-occipital cortices 200-600 msec after the cue onset, possibly reflecting cross-modal modulation of the dorsal visual pathway during audiospatial attention. Comparisons of cortical power patterns also revealed significant increases of sustained right medial frontal cortex theta power, right dorsolateral pFC and anterior insula/inferior frontal cortex beta power, and medial parietal cortex and posterior cingulate cortex gamma activity after cued versus novelty-triggered orienting (600-1400 msec). Our results reveal sustained oscillatory patterns associated with voluntary engagement of auditory spatial attention, with the frontoparietal and temporal gamma increases being best predictors of subsequent behavioral performance.

Whole-head rapid fMRI acquisition using echo-shifted magnetic resonance inverse imaging.

The acquisition time of BOLD contrast functional MRI (fMRI) data with whole-brain coverage typically requires a sampling rate of one volume in 1-3s. Although the volumetric sampling time of a few seconds is adequate for measuring the sluggish hemodynamic response (HDR) to neuronal activation, faster sampling of fMRI might allow for monitoring of rapid physiological fluctuations and detection of subtle neuronal activation timing information embedded in BOLD signals. Previous studies utilizing a highly accelerated volumetric MR inverse imaging (InI) technique have provided a sampling rate of one volume per 100 ms with 5mm spatial resolution. Here, we propose a novel modification of this technique, the echo-shifted InI, which allows TE to be longer than TR, to measure BOLD fMRI at an even faster sampling rate of one volume per 25 ms with whole-brain coverage. Compared with conventional EPI, echo-shifted InI provided an 80-fold speedup with similar spatial resolution and less than 2-fold temporal SNR loss. The capability of echo-shifted InI to detect HDR timing differences was tested empirically. At the group level (n=6), echo-spaced InI was able to detect statistically significant HDR timing differences of as low as 50 ms in visual stimulus presentation. At the level of individual subjects, significant differences in HDR timing were detected for 400 ms stimulus-onset differences. Our results also show that the temporal resolution of 25 ms is necessary for maintaining the temporal detecting capability at this level. With the capabilities of being able to distinguish the timing differences in the millisecond scale, echo-shifted InI could be a useful fMRI tool for obtaining temporal information at a time scale closer to that of neuronal dynamics.

fMRI hemodynamics accurately reflects neuronal timing in the human brain measured by MEG.

Neuronal activation sequence information is essential for understanding brain functions. Extracting such timing information from blood oxygenation level dependent (BOLD) fMRI is confounded by interregional neurovascular differences and poorly understood relations between BOLD and electrophysiological response delays. Here, we recorded whole-head BOLD fMRI at 100 ms resolution and magnetoencephalography (MEG) during a visuomotor reaction-time task. Both methods detected the same activation sequence across five regions, from visual towards motor cortices, with linearly correlated interregional BOLD and MEG response delays. The smallest significant interregional BOLD delay was 100 ms; all delays ≥400 ms were significant. Switching the order of external events reversed the sequence of BOLD activations, indicating that interregional neurovascular differences did not confound the results. This may open new avenues for using fMRI to follow rapid activation sequences in the brain.

Dynamic cortical activity during the perception of three-dimensional object shape from two-dimensional random-dot motion.

Recent neuroimaging studies implicate that both the dorsal and ventral visual pathways, as well as the middle temporal (MT) areas which are critical for the perception of visual motion, are involved in the perception of three-dimensional (3D) structure from two-dimensional (2D) motion (3D-SFM). However, the neural dynamics underlying the reconstruction of a 3D object from 2D optic flow is not known. Here we combined magnetoencephalography (MEG) and functional MRI (fMRI) measurements to investigate the spatiotemporal brain dynamics during 3D-SFM. We manipulated parametrically the coherence of randomly moving groups of dots to create different levels of 3D perception and to study the associated changes in brain activity. At different latencies, the posterior infero-temporal (pIT), the parieto-occipital (PO), and the intraparietal (IP) regions showed increased neural activity during highly coherent motion conditions in which subjects perceived a robust 3D object. Causality analysis between these regions indicated significant causal influence from IP to pIT and from pIT to PO only in conditions where subjects perceived a robust 3D object. Current results suggest that the perception of a 3D object from 2D motion includes integration of global motion and 3D mental image processing, as well as object recognition that are accomplished by interactions between the dorsal and ventral visual pathways.

Ultrafast inverse imaging techniques for fMRI.

Inverse imaging (InI) supercharges the sampling rate of traditional functional MRI 10-100 fold at a cost of a moderate reduction in spatial resolution. The technique is inspired by similarities between multi-sensor magnetoencephalography (MEG) and highly parallel radio-frequency (RF) MRI detector arrays. Using presently available 32-channel head coils at 3T, InI can be sampled at 10 Hz and provides about 5-mm cortical spatial resolution with whole-brain coverage. Here we discuss the present applications of InI, as well as potential future challenges and opportunities in further improving its spatiotemporal resolution and sensitivity. InI may become a helpful tool for clinicians and neuroscientists for revealing the complex dynamics of brain functions during task-related and resting states.

Physiological noise reduction using volumetric functional magnetic resonance inverse imaging.

Physiological noise arising from a variety of sources can significantly degrade the detection of task-related activity in BOLD-contrast fMRI experiments. If whole head spatial coverage is desired, effective suppression of oscillatory physiological noise from cardiac and respiratory fluctuations is quite difficult without external monitoring, since traditional EPI acquisition methods cannot sample the signal rapidly enough to satisfy the Nyquist sampling theorem, leading to temporal aliasing of noise. Using a combination of high speed magnetic resonance inverse imaging (InI) and digital filtering, we demonstrate that it is possible to suppress cardiac and respiratory noise without auxiliary monitoring, while achieving whole head spatial coverage and reasonable spatial resolution. Our systematic study of the effects of different moving average (MA) digital filters demonstrates that a MA filter with a 2 s window can effectively reduce the variance in the hemodynamic baseline signal, thereby achieving 57%-58% improvements in peak z-statistic values compared to unfiltered InI or spatially smoothed EPI data (FWHM = 8.6 mm). In conclusion, the high temporal sampling rates achievable with InI permit significant reductions in physiological noise using standard temporal filtering techniques that result in significant improvements in hemodynamic response estimation.

Reconstruction of MRI data encoded by multiple nonbijective curvilinear magnetic fields.

Parallel imaging technique using localized gradients (PatLoc) uses the combination of surface gradient coils generating nonbijective curvilinear magnetic fields for spatial encoding. PatLoc imaging using one pair of multipolar spatial encoding magnetic fields (SEMs) has two major caveats: (1) The direct inversion of the encoding matrix requires exact determination of multiple locations which are ambiguously encoded by the SEMs. (2) Reconstructed images have a prominent loss of spatial resolution at the center of field-of-view using a symmetric coil array for signal detection. This study shows that a PatLoc system actually has a higher degree of freedom in spatial encoding to mitigate the two challenges mentioned above. Specifically, a PatLoc system can generate not only multipolar but also linear SEMs, which can be used to reduce the loss of spatial resolution at the field-of-view center. Here, we present an efficient and generalized image reconstruction method for PatLoc imaging using multiple SEMs without explicitly identifying the locations where SEM encoding is not unique. Reconstructions using simulations and empirical experimental data are compared with those using conventional linear gradients to demonstrate that the general combination of SEMs can improve image reconstructions.

Multimodal functional imaging using fMRI-informed regional EEG/MEG source estimation.

We propose a novel method, fMRI-Informed Regional Estimation (FIRE), which utilizes information from fMRI in E/MEG source reconstruction. FIRE takes advantage of the spatial alignment between the neural and the vascular activities, while allowing for substantial differences in their dynamics. Furthermore, with a region-based approach, FIRE estimates the model parameters for each region independently. Hence, it can be efficiently applied on a dense grid of source locations. The optimization procedure at the core of FIRE is related to the re-weighted minimum-norm algorithms. The weights in the proposed approach are computed from both the current source estimates and fMRI data, leading to robust estimates in the presence of silent sources in either fMRI or E/MEG measurements. We employ a Monte Carlo evaluation procedure to compare the proposed method to several other joint E/MEG-fMRI algorithms. Our results show that FIRE provides the best trade-off in estimation accuracy between the spatial and the temporal accuracy. Analysis using human E/MEG-fMRI data reveals that FIRE significantly reduces the ambiguities in source localization present in the minimum-norm estimates, and that it accurately captures activation timing in adjacent functional regions.

K-space reconstruction of magnetic resonance inverse imaging (K-InI) of human visuomotor systems.

Using simultaneous measurements from multiple channels of a radio-frequency coil array, magnetic resonance inverse imaging (InI) can achieve ultra-fast dynamic functional imaging of the human with whole-brain coverage and a good spatial resolution. Mathematically, the InI reconstruction is a generalization of parallel MRI (pMRI), which includes image space and k-space reconstructions. Because of the auto-calibration technique, the pMRI k-space reconstruction offers more robust and adaptive reconstructions compared to the image space algorithm. Here we present the k-space InI (K-InI) reconstructions to reconstruct the highly accelerated BOLD-contrast fMRI data of the human brain to achieve 100 ms temporal resolution. Simulations show that K-InI reconstructions can offer 3D image reconstructions at each time frame with reasonable spatial resolution, which cannot be obtained using the previously proposed image space minimum-norm estimates (MNE) or linear constraint minimum variance (LCMV) spatial filtering reconstructions. The InI reconstructions of in vivo BOLD-contrast fMRI data during a visuomotor task show that K-InI offer 3 to 5 fold more sensitive detection of the brain activation than MNE and a comparable detection sensitivity to the LCMV reconstructions. The group average of the high temporal resolution K-InI reconstructions of the hemodynamic response also shows a relative onset timing difference between the visual (first) and somatomotor (second) cortices by 400 ms (600 ms time-to-peak timing difference). This robust and sensitive K-InI reconstruction can be applied to dynamic MRI acquisitions using a large-n coil array to improve the spatiotemporal resolution.

Propagation of epileptic spikes reconstructed from spatiotemporal magnetoencephalographic and electroencephalographic source analysis.

The purpose of this study is to assess the accuracy of spatiotemporal source analysis of magnetoencephalography (MEG) and scalp electroencephalography (EEG) for representing the propagation of frontotemporal spikes in patients with partial epilepsy. This study focuses on frontotemporal spikes, which are typically characterized by a preceding anterior temporal peak followed by an ipsilateral inferior frontal peak. Ten patients with frontotemporal spikes on MEG/EEG were studied. We analyzed the propagation of temporal to frontal epileptic spikes on both MEG and EEG independently by using a cortically constrained minimum norm estimate (MNE). Spatiotemporal source distribution of each spike was obtained on the cortical surface derived from the patient's MRI. All patients underwent an extraoperative intracranial EEG (IEEG) recording covering temporal and frontal lobes after presurgical evaluation. We extracted source waveforms of MEG and EEG from the source distribution of interictal spikes at the sites corresponding to the location of intracranial electrodes. The time differences of the ipsilateral temporal and frontal peaks as obtained by MEG, EEG and IEEG were statistically compared in each patient. In all patients, MEG and IEEG showed similar time differences between temporal and frontal peaks. The time differences of EEG spikes were significantly smaller than those of IEEG in nine of ten patients. Spatiotemporal analysis of MEG spikes models the time course of frontotemporal spikes as observed on IEEG more adequately than EEG in our patients. Spatiotemporal source analysis may be useful for planning epilepsy surgery, by predicting the pattern of IEEG spikes.

Onset timing of cross-sensory activations and multisensory interactions in auditory and visual sensory cortices.

Here we report early cross-sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300-ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within-modality and cross-sensory activations. fMRI cross-sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects the influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl's gyrus) the onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross-sensory activations thus started later than sensory-specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross-sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30-35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory and 74 ms in the visual cortex, i.e., 3-21 ms after inputs from the two modalities converged.

Cancellation of EEG and MEG signals generated by extended and distributed sources.

Extracranial patterns of scalp potentials and magnetic fields, as measured with electro- and magnetoencephalography (EEG, MEG), are spatially widespread even when the underlying source in the brain is focal. Therefore, loss in signal magnitude due to cancellation is expected when multiple brain regions are simultaneously active. We characterized these cancellation effects in EEG and MEG using a forward model with sources constrained on an anatomically accurate reconstruction of the cortical surface. Prominent cancellation was found for both EEG and MEG in the case of multiple randomly distributed source dipoles, even when the number of simultaneous dipoles was small. Substantial cancellation occurred also for locally extended patches of simulated activity, when the patches extended to opposite walls of sulci and gyri. For large patches, a difference between EEG and MEG cancellation was seen, presumably due to selective cancellation of tangentially vs. radially oriented sources. Cancellation effects can be of importance when electrophysiological data are related to hemodynamic measures. Furthermore, the selective cancellation may be used to explain some observed differences between EEG and MEG in terms of focal vs. widespread cortical activity.

Sensitivity of MEG and EEG to source orientation.

An important difference between magnetoencephalography (MEG) and electroencephalography (EEG) is that MEG is insensitive to radially oriented sources. We quantified computationally the dependency of MEG and EEG on the source orientation using a forward model with realistic tissue boundaries. Similar to the simpler case of a spherical head model, in which MEG cannot see radial sources at all, for most cortical locations there was a source orientation to which MEG was insensitive. The median value for the ratio of the signal magnitude for the source orientation of the lowest and the highest sensitivity was 0.06 for MEG and 0.63 for EEG. The difference in the sensitivity to the source orientation is expected to contribute to systematic differences in the signal-to-noise ratio between MEG and EEG.

White matter integrity and pictorial reasoning in high-functioning children with autism.

The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response times (RT) on a pictorial reasoning task under three conditions: visuospatial, V, semantic, S, and V+S, a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion-weighted images were collected from HFA and CTRL participants, matched on age and IQ, and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (S) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL. Performance in visuospatial reasoning (V, V+S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL. Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically developing children, whereas autistic cognition may rely more on visuospatial processing networks.

Short-term plasticity in auditory cognition.

Converging lines of evidence suggest that auditory system short-term plasticity can enable several perceptual and cognitive functions that have been previously considered as relatively distinct phenomena. Here we review recent findings suggesting that auditory stimulation, auditory selective attention and cross-modal effects of visual stimulation each cause transient excitatory and (surround) inhibitory modulations in the auditory cortex. These modulations might adaptively tune hierarchically organized sound feature maps of the auditory cortex (e.g. tonotopy), thus filtering relevant sounds during rapidly changing environmental and task demands. This could support auditory sensory memory, pre-attentive detection of sound novelty, enhanced perception during selective attention, influence of visual processing on auditory perception and longer-term plastic changes associated with perceptual learning.