A computational paradigm for real-time MEG neurofeedback for dynamic allocation of spatial attention.

BACKGROUND: Neurofeedback aids volitional control of one's own brain activity using non-invasive recordings of brain activity. The applications of neurofeedback include improvement of cognitive performance and treatment of various psychiatric and neurological disorders. During real-time magnetoencephalography (rt-MEG), sensor-level or source-localized brain activity is measured and transformed into a visual feedback cue to the subject. Recent real-time fMRI (rt-fMRI) neurofeedback studies have used pattern recognition techniques to decode and train a brain state to link brain activities and cognitive behaviors. Here, we utilize the real-time decoding technique similar to ones employed in rt-fMRI to analyze time-varying rt-MEG signals. RESULTS: We developed a novel rt-MEG method, state-based neurofeedback (sb-NFB), to decode a time-varying brain state, a state signal, from which timings are extracted for neurofeedback training. The approach is entirely data-driven: it uses sensor-level oscillatory activity to find relevant features that best separate the targeted brain states. In a psychophysical task of spatial attention switching, we trained five young, healthy subjects using the sb-NFB method to decrease the time necessary for switch spatial attention from one visual hemifield to the other (referred to as switch time). Training resulted in a decrease in switch time with training. We saw that the activity targeted by the training involved proportional changes in alpha and beta-band oscillations, in sensors at the occipital and parietal regions. We also found that the state signal that encodes whether subjects attend to the left or right visual field effectively switches consistently with the task. CONCLUSION: We demonstrated the use of the sb-NFB method when the subject learns to increase the speed of shifting covert spatial attention from one visual field to the other. The sb-NFB method can target timing features that would otherwise also include extraneous features such as visual detection and motor response in a simple reaction time task.

Differential cortical activation during the perception of moving objects along different trajectories.

Detection of 3D object-motion trajectories depends on the integration of two distinct visual cues: translational displacement and looming. Electrophysiological studies have identified distinct neuronal populations, whose activity depends on the precise motion cues present in the stimulus. This distinction, however, has been less clear in humans, and it is confounded by differences in the behavioral task being performed. We analyzed whole-brain fMRI, while subjects performed a common time-to-arrival task for objects moving along three trajectories: moving directly towards the observer (collision course), with trajectories parallel to the line of sight (passage course), and with trajectories perpendicular to the line of sight (gap closure). We found that there was substantial overlap in the pattern of activation associated with each of the three tasks, with differences among conditions limited to the human motion area (hMT+), which showed greater activation extent in the gap closure condition than for either collision or passage courses. These results support a common substrate for temporal judgments of an object's time-to-arrival, wherein the special cases of object motion directly toward, or perpendicular to, the observer represent two extremes within the broader continuum of 3D passage trajectories relative to the observer.

Peripheral visual localization is degraded by globally incongruent auditory-spatial attention cues.

Global auditory-spatial orienting cues help the detection of weak visual stimuli, but it is not clear whether crossmodal attention cues also enhance the resolution of visuospatial discrimination. Here, we hypothesized that if anywhere, crossmodal modulations of visual localization should emerge in the periphery where the receptive fields are large. Subjects were presented with trials where a Visual Target, defined by a cluster of low-luminance dots, was shown for 220 ms at 25°-35° eccentricity in either the left or right hemifield. The Visual Target was either Uncued or it was presented 250 ms after a crossmodal Auditory Cue that was simulated either from the same or the opposite hemifield than the Visual Target location. After a whole-screen visual mask displayed for 800 ms, a pair of vertical Reference Bars was presented ipsilateral to the Visual Target. In a two-alternative forced choice task, subjects were asked to determine which of these two bars was closer to the center of the Visual Target. When the Auditory Cue and Visual Target were hemispatially incongruent, the speed and accuracy of visual localization performance was significantly impaired. However, hemispatially congruent Auditory Cues did not improve the localization of Visual Targets when compared to the Uncued condition. Further analyses suggested that the crossmodal Auditory Cues decreased the sensitivity (d') of the Visual Target localization without affecting post-perceptual decision biases. Our results suggest that in the visual periphery, the detrimental effect of hemispatially incongruent Auditory Cues is far greater than the benefit produced by hemispatially congruent cues. Our working hypothesis for future studies is that auditory-spatial attention cues suppress irrelevant visual locations in a global fashion, without modulating the local visual precision at relevant sites.

Maturation trajectories of cortical resting-state networks depend on the mediating frequency band.

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13-30 Hz) and gamma (31-80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development.

Motion sequence analysis in the presence of figural cues.

The perception of 3D structure in dynamic sequences is believed to be subserved primarily through the use of motion cues. However, real-world sequences contain many figural shape cues besides the dynamic ones. We hypothesize that if figural cues are perceptually significant during sequence analysis, then inconsistencies in these cues over time would lead to percepts of non-rigidity in sequences showing physically rigid objects in motion. We develop an experimental paradigm to test this hypothesis and present results with two patients with impairments in motion perception due to focal neurological damage, as well as two control subjects. Consistent with our hypothesis, the data suggest that figural cues strongly influence the perception of structure in motion sequences, even to the extent of inducing non-rigid percepts in sequences where motion information alone would yield rigid structures. Beyond helping to probe the issue of shape perception, our experimental paradigm might also serve as a possible perceptual assessment tool in a clinical setting.

Reorganization of retinotopic maps after occipital lobe infarction.

We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT(+)) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.

Population anisotropy in area MT explains a perceptual difference between near and far disparity motion segmentation.

Segmentation of the visual scene into relevant object components is a fundamental process for successfully interacting with our surroundings. Many visual cues, including motion and binocular disparity, support segmentation, yet the mechanisms using these cues are unclear. We used a psychophysical motion discrimination task in which noise dots were displaced in depth to investigate the role of segmentation through disparity cues in visual motion stimuli (experiment 1). We found a subtle, but significant, bias indicating that near disparity noise disrupted the segmentation of motion more than equidistant far disparity noise. A control experiment showed that the near-far difference could not be attributed to attention (experiment 2). To account for the near-far bias, we constructed a biologically constrained model using recordings from neurons in the middle temporal area (MT) to simulate human observers' performance on experiment 1. Performance of the model of MT neurons showed a near-disparity skew similar to that shown by human observers. To isolate the cause of the skew, we simulated performance of a model containing units derived from properties of MT neurons, using phase-modulated Gabor disparity tuning. Using a skewed-normal population distribution of preferred disparities, the model reproduced the elevated motion discrimination thresholds for near-disparity noise, whereas a skewed-normal population of phases (creating individually asymmetric units) did not lead to any performance skew. Results from the model suggest that the properties of neurons in area MT are computationally sufficient to perform disparity segmentation during motion processing and produce similar disparity biases as those produced by human observers.

Two mechanisms for optic flow and scale change processing of looming.

The detection of looming, the motion of objects in depth, underlies many behavioral tasks, including the perception of self-motion and time-to-collision. A number of studies have demonstrated that one of the most important cues for looming detection is optic flow, the pattern of motion across the retina. Schrater et al. have suggested that changes in spatial frequency over time, or scale changes, may also support looming detection in the absence of optic flow (P. R. Schrater, D. C. Knill, & E. P. Simoncelli, 2001). Here we used an adaptation paradigm to determine whether the perception of looming from optic flow and scale changes is mediated by single or separate mechanisms. We show first that when the adaptation and test stimuli were the same (both optic flow or both scale change), observer performance was significantly impaired compared to a dynamic (non-motion, non-scale change) null adaptation control. Second, we found no evidence of cross-cue adaptation, either from optic flow to scale change, or vice versa. Taken together, our data suggest that optic flow and scale changes are processed by separate mechanisms, providing multiple pathways for the detection of looming.

Auditory cues facilitate object movement processing in human extrastriate visual cortex during simulated self-motion: A pilot study.

Visual segregation of moving objects is a considerable computational challenge when the observer moves through space. Recent psychophysical studies suggest that directionally congruent, moving auditory cues can substantially improve parsing object motion in such settings, but the exact brain mechanisms and visual processing stages that mediate these effects are still incompletely known. Here, we utilized multivariate pattern analyses (MVPA) of MRI-informed magnetoencephalography (MEG) source estimates to examine how crossmodal auditory cues facilitate motion detection during the observer's self-motion. During MEG recordings, participants identified a target object that moved either forward or backward within a visual scene that included nine identically textured objects simulating forward observer translation. Auditory motion cues 1) improved the behavioral accuracy of target localization, 2) significantly modulated the MEG source activity in the areas V2 and human middle temporal complex (hMT+), and 3) increased the accuracy at which the target movement direction could be decoded from hMT+ activity using MVPA. The increase of decoding accuracy by auditory cues in hMT+ was significant also when superior temporal activations in or near auditory cortices were regressed out from the hMT+ source activity to control for source estimation biases caused by point spread. Taken together, these results suggest that parsing object motion from self-motion-induced optic flow in the human extrastriate visual cortex can be facilitated by crossmodal influences from auditory system.

Effect of Residual Interatrial Shunt on Migraine Burden After Transcatheter Closure of Patent Foramen Ovale.

OBJECTIVES: This study sought to evaluate the long-term effect of transcatheter patent foramen ovale (PFO) closure on migraineurs with and without aura and examine the effect of residual right-to-left shunt. BACKGROUND: Many studies reported improvement in migraine symptoms after PFO closure, yet randomized trials failed to reach its clinical endpoints. METHODS: The study retrospectively analyzed data from 474 patients who underwent transcatheter PFO closure at Massachusetts General Hospital. Patients completed a migraine burden questionnaire at baseline and at follow-up. Migraine severity is reported as migraine frequency (days/month), average duration (min), and migraine burden (days × min/month). Improvement following closure was defined as complete abolishment of symptoms or >50% reduction in migraine burden. RESULTS: A total of 110 migraineurs who underwent PFO closure were included; 77.0% had aura and 23.0% were without aura, and 91.0% had a cryptogenic stroke. During long-term median follow-up of 3.2 (interquartile range: 2.1 to 4.9) years, there was a significant improvement in migraine symptoms in migraineurs with or without aura. Migraine burden was reduced by >50% in 87.0% of patients, and symptoms were completely abolished in 48%. Presence of aura was associated with abolishment of migraine (odds ratio: 4.30; 95% confidence interval: 1.50 to 12.30; p = 0.006). At 6 months after PFO closure, residual right-to-left shunt was present in 26% of patients. Absence of right-to-left shunt was associated with improvement in migraine burden by >50% (odds ratio: 4.60; 95% confidence interval: 1.30 to 16.10; p = 0.017). CONCLUSIONS: Long-term follow-up after transcatheter PFO closure was associated with significant improvement in migraine burden. Aura was a predictor of abolishing symptoms. Absence of residual right-to-left shunt was a predictor of significant reduction in migraine burden.

Mapping the signal-to-noise-ratios of cortical sources in magnetoencephalography and electroencephalography.

Although magnetoencephalography (MEG) and electroencephalography (EEG) have been available for decades, their relative merits are still debated. We examined regional differences in signal-to-noise-ratios (SNRs) of cortical sources in MEG and EEG. Data from four subjects were used to simulate focal and extended sources located on the cortical surface reconstructed from high-resolution magnetic resonance images. The SNR maps for MEG and EEG were found to be complementary. The SNR of deep sources was larger in EEG than in MEG, whereas the opposite was typically the case for superficial sources. Overall, the SNR maps were more uniform for EEG than for MEG. When using a noise model based on uniformly distributed random sources on the cortex, the SNR in MEG was found to be underestimated, compared with the maps obtained with noise estimated from actual recorded MEG and EEG data. With extended sources, the total area of cortex in which the SNR was higher in EEG than in MEG was larger than with focal sources. Clinically, SNR maps in a patient explained differential sensitivity of MEG and EEG in detecting epileptic activity. Our results emphasize the benefits of recording MEG and EEG simultaneously.

An effect of relative motion on trajectory discrimination.

Psychophysical studies point to the existence of specialized mechanisms sensitive to the relative motion between an object and its background. Such mechanisms would seem ideal for the motion-based segmentation of objects; however, their properties and role in processing the visual scene remain unclear. Here we examine the contribution of relative motion mechanisms to the processing of object trajectory. In a series of four psychophysical experiments we examine systematically the effects of relative direction and speed differences on the perceived trajectory of an object against a moving background. We show that background motion systematically influences the discrimination of object direction. Subjects' ability to discriminate direction was consistently better for objects moving opposite a translating background than for objects moving in the same direction as the background. This effect was limited to the case of a translating background and did not affect perceived trajectory for more complex background motions associated with self-motion. We interpret these differences as providing support for the role of relative motion mechanisms in the segmentation and representation of object motions that do not occlude the path of an observer's self-motion.

Improving the Nulling Beamformer Using Subspace Suppression.

Magnetoencephalography (MEG) captures the magnetic fields generated by neuronal current sources with sensors outside the head. In MEG analysis these current sources are estimated from the measured data to identify the locations and time courses of neural activity. Since there is no unique solution to this so-called inverse problem, multiple source estimation techniques have been developed. The nulling beamformer (NB), a modified form of the linearly constrained minimum variance (LCMV) beamformer, is specifically used in the process of inferring interregional interactions and is designed to eliminate shared signal contributions, or cross-talk, between regions of interest (ROIs) that would otherwise interfere with the connectivity analyses. The nulling beamformer applies the truncated singular value decomposition (TSVD) to remove small signal contributions from a ROI to the sensor signals. However, ROIs with strong crosstalk will have high separating power in the weaker components, which may be removed by the TSVD operation. To address this issue we propose a new method, the nulling beamformer with subspace suppression (NBSS). This method, controlled by a tuning parameter, reweights the singular values of the gain matrix mapping from source to sensor space such that components with high overlap are reduced. By doing so, we are able to measure signals between nearby source locations with limited cross-talk interference, allowing for reliable cortical connectivity analysis between them. In two simulations, we demonstrated that NBSS reduces cross-talk while retaining ROIs' signal power, and has higher separating power than both the minimum norm estimate (MNE) and the nulling beamformer without subspace suppression. We also showed that NBSS successfully localized the auditory M100 event-related field in primary auditory cortex, measured from a subject undergoing an auditory localizer task, and suppressed cross-talk in a nearby region in the superior temporal sulcus.

Aging Impairs Audiovisual Facilitation of Object Motion Within Self-Motion.

The presence of a moving sound has been shown to facilitate the detection of an independently moving visual target embedded among an array of identical moving objects simulating forward self-motion (Calabro et al., Proc. R. Soc. B, 2011). Given that the perception of object motion within self-motion declines with aging, we investigated whether older adults can also benefit from the presence of a congruent dynamic sound when detecting object motion within self-motion. Visual stimuli consisted of nine identical spheres randomly distributed inside a virtual rectangular prism. For 1 s, all the spheres expanded outward simulating forward observer translation at a constant speed. One of the spheres (the target) had independent motion either approaching or moving away from the observer at three different speeds. In the visual condition, stimuli contained no sound. In the audiovisual condition, the visual stimulus was accompanied by a broadband noise sound co-localized with the target, whose loudness increased or decreased congruent with the target's direction. Participants reported which of the spheres had independent motion. Younger participants showed higher target detection accuracy in the audiovisual compared to the visual condition at the slowest speed level. Older participants showed overall poorer target detection accuracy than the younger participants, but the presence of the sound had no effect on older participants' target detection accuracy at either speed level. These results indicate that aging may impair cross-modal integration in some contexts. Potential reasons for the absence of auditory facilitation in older adults are discussed.

Partial volume correction for PET quantification and its impact on brain network in Alzheimer's disease.

Amyloid positron emission tomography (PET) imaging is a valuable tool for research and diagnosis in Alzheimer's disease (AD). Partial volume effects caused by the limited spatial resolution of PET scanners degrades the quantitative accuracy of PET image. In this study, we have applied a method to evaluate the impact of a joint-entropy based partial volume correction (PVC) technique on brain networks learned from a clinical dataset of AV-45 PET image and compare network properties of both uncorrected and corrected image-based brain networks. We also analyzed the region-wise SUVRs of both uncorrected and corrected images. We further performed classification tests on different groups using the same set of algorithms with same parameter settings. PVC has sometimes been avoided due to increased noise sensitivity in image registration and segmentation, however, our results indicate that appropriate PVC may enhance the brain network structure analysis for AD progression and improve classification performance.

Deficits of motion integration and segregation in patients with unilateral extrastriate lesions.

Functional neuroimaging in human subjects and single cell recordings in monkeys show that several extra-striate visual areas are activated by visual motion. However, the extent to which different types of motion are processed in different regions remains unclear, although neuropsychological studies of patients with circumscribed lesions hint at regional specialization. We, therefore, studied four patients with unilateral damage to different regions of extrastriate visual cortex on a series of visual discrimination tasks that required them, to a different extent, to integrate local motion signals in order to correctly perceive the direction of global motion. Performance was assessed psychophysically and compared with that of control subjects and with the patients' performance with stimuli presented in the visual field ipsilateral to the lesion. The results indicate considerable regional specialization in extra-striate regions for different aspects of motion processing, namely the largest displacement from frame to frame (D-max) that can sustain perception of coherent motion; perception of relative speed; the amount of coherent motion needed to sustain a percept of global motion in a particular direction; the detection of discontinuities within a moving display; the extraction of form from motion. It was also clear that a defect in local motion, i.e. D-max, can be overcome by integrating local motion signals over a longer period of time. Although no patient suffered from only one defect, the overall pattern of results strongly supports the notion of regional specialization for different aspects of motion processing.

Psychophysical evidence for a radial motion bias in complex motion discrimination.

In a graded motion pattern task we measured observers' ability to discriminate small changes in the global direction of complex motion patterns. Performance varied systematically as a function of the test motion (radial, circular, or spiral) with thresholds for radial motions significantly lower than for circular motions. Thresholds for spiral motions were intermediate. In all cases thresholds were lower than for direction discrimination using planar motions and increased with removal of the radial speed gradient, consistent with the use of motion pattern specific mechanisms that integrate motion along complex trajectories. The radial motion bias and preference for speed gradients observed here is similar to the preference for expanding motions and speed gradients reported in cortical area MSTd, and may suggest the presence of comparable neural mechanisms in the human visual motion system.

Can spatial and temporal motion integration compensate for deficits in local motion mechanisms?

We studied the motion perception of a patient, AMG, who had a lesion in the left occipital lobe centered on visual areas V3 and V3A, with involvement of underlying white matter. As shown by a variety of psychophysical tests involving her perception of motion, the patient was impaired at motion discriminations that involved the detection of small displacements of random-dot displays, including local speed discrimination. However, she was unimpaired on tests that required spatial and temporal integration of moving displays, such as motion coherence. The results indicate that she had a specific impairment of the computation of local but not global motion and that she could not integrate motion information across different spatial scales. Such a specific impairment has not been reported before.

First-order and second-order motion: neurological evidence for neuroanatomically distinct systems.

An unresolved issue in visual motion perception is how distinct are the processes underlying 'first-order' and 'second-order' motion. The former is defined by spatio-temporal variations of luminance and the latter by spatio-temporal variations in other image attributes such as contrast or depth, for example. Using neuroimaging and psychophysics we present data from four neurological patients with unilateral and mostly cortical infarcts, which strongly suggest that first- and second-order motion have a different neural substrate. We found that from the early stages of processing, these two types of motions are mediated by two distinct pathways: first-order motion is carried out by mechanisms along the dorsal pathway in the occipital lobe, while the second-order motion by mechanisms mostly along the ventral pathway. The data reported here also suggest that different cortical regions may be in charge of processing direction-discrimination in second-order motion defined by different second-order attributes.

Is precise discrimination of low level motion needed for heading discrimination?

Normal observers judge heading well both when moving in a straight line and when moving along a curved path. Judgments of curved path motion require depth variations in the scene while judgments of straight line heading (pure translation) do not. Here we show that a stroke patient who is impaired in low level 2D motion discrimination tasks and cannot accurately judge 3D structure from motion can accurately judge heading for straight line self-motion. This patient is impaired in judgments of curved path self-motion. This suggests that accurate heading judgments for observer translation do not require accurate 2D motion perception or 3D reconstruction of the scene. Judgments of curved path motion appear more dependent on accurate 2D motion perception.