Gijs Plomp

Dynamic directed interictal connectivity in left and right temporal lobe epilepsy

There is increasing evidence that epileptic activity involves widespread brain networks rather than single sources and that these networks contribute to interictal brain dysfunction. We investigated the fast‐varying behavior of epileptic networks during interictal spikes in right and left temporal lobe epilepsy (RTLE and LTLE) at a whole‐brain scale using directed connectivity.

Decoding stimulus-related information from single-trial EEG responses based on voltage topographies

Neuroimaging studies typically compare experimental conditions using average brain responses, thereby overlooking the stimulus-related information conveyed by distributed spatio-temporal patterns of single-trial responses. Here, we take advantage of this rich information at a single-trial level to decode stimulus-related signals in two event-related potential (ERP) studies. Our method models the statistical distribution of the voltage topographies with a Gaussian Mixture Model (GMM), which reduces the dataset to a number of representative voltage topographies. The degree of presence of these topographies across trials at specific latencies is then used to classify experimental conditions. We tested the algorithm using a cross-validation procedure in two independent EEG datasets. In the first ERP study, we classified left- versus right-hemifield checkerboard stimuli for upper and lower visual hemifields. In a second ERP study, when functional differences cannot be assumed, we classified initial versus repeated presentations of visual objects. With minimal a priori information, the GMM model provides neurophysiologically interpretable features - vis a vis voltage topographies - as well as dynamic information about brain function. This method can in principle be applied to any ERP dataset testing the functional relevance of specific time periods for stimulus processing, the predictability of subjects behavior and cognitive states, and the discrimination between healthy and clinical populations.

The physiological plausibility of time-varying Granger-causal modeling: normalization and weighting by spectral power.

Time-varying connectivity methods are increasingly used to study directed interactions between brain regions from electrophysiological signals. These methods often show good results in simulated data but it is unclear to what extent connectivity results obtained from real data are physiologically plausible. Here we introduce a benchmark approach using multichannel somatosensory evoked potentials (SEPs) measured across rat cortex, where the structural and functional connectivity is relatively simple and well-understood. Rat SEPs to whisker stimulation are exclusively initiated by contralateral primary sensory cortex (S1), at known latencies, and with activity spread from S1 to specific cortical regions. This allows for a comparison of time-varying connectivity measures according to fixed criteria. We thus evaluated the performance of time-varying Partial Directed Coherence (PDC) and the Directed Transfer Function (DTF), comparing row- and column-wise normalization and the effect of weighting by the power spectral density (PSD). The benchmark approach revealed clear differences between methods in terms of physiological plausibility, effect size and temporal resolution. The results provide a validation of time-varying directed connectivity methods in an animal model and suggest a driving role for ipsilateral S1 in the later part of the SEP. The benchmark SEP dataset is made freely available.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study

In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger‐causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls.

Electrical source dynamics in three functional localizer paradigms.

The visual cortex exhibits functional specialization that can be routinely demonstrated using hemodynamic measures like fMRI and PET. To understand the dynamic nature of cortical processes, however, source imaging with a high temporal resolution is necessary. Here, we asked how well distributed EEG source localization (LAURA) identifies functionally specialized visual processes. We tested three stimulus paradigms commonly used in fMRI with the aim to localize striate cortex, motion-sensitive areas, and face-sensitive areas. EEG source localization showed initial activations in striate and extra-striate areas at around 70ms after stimulus onset. These were quickly followed by extensive cortical, as well as subcortical activation. Functional motion and face-selective areas were localized with margins of below 2cm, at around 170 and 150ms, respectively. The results furthermore show for the first time that the C1 component has generators in the insula and frontal eye fields, but also in subcortical areas like the parahippocampus and the thalamus.

Neural correlates of visual crowding

In visual crowding, target discrimination strongly deteriorates when flanking elements are added. We have recently shown that crowding cannot be explained by simple low-level interactions and that grouping is a key component instead. We presented a vernier flanked by arrays of vertical lines. When the flankers had the same lengths as the vernier, offset discrimination was strongly impaired. When longer flankers were presented, crowding was weaker. We proposed that crowding is strong when the flankers group with the target (equal length flankers). When the target segregates from the flankers, crowding is weaker (long flankers). To understand the neurophysiological mechanisms of grouping in crowding, here, we adapted the above vernier paradigm to a high-density EEG study. The P1 component reflected basic stimulus characteristics (flanker length) but not crowding. Crowding emerged slowly and manifested as a suppression of the N1 component (after 180ms). Using inverse solutions, we found that the N1 suppression was caused by reduced neural activity in high-level visual areas such as the lateral occipital cortex. Our results suggest that crowding occurs when elements are grouped into wholes, a process reflected by the N1 component.

Electrophysiological Evidence for Ventral Stream Deficits in Schizophrenia Patients

Schizophrenic patients suffer from many deficits including visual, attentional, and cognitive ones. Visual deficits are of particular interest because they are at the fore-end of information processing and can provide clear examples of interactions between sensory, perceptual, and higher cognitive functions. Visual deficits in schizophrenic patients are often attributed to impairments in the dorsal (where) rather than the ventral (what) stream of visual processing. We used a visual-masking paradigm in which patients and matched controls discriminated small vernier offsets. We analyzed the evoked electroencephalography (EEG) responses and applied distributed electrical source imaging techniques to estimate activity differences between conditions and groups throughout the brain. Compared with controls, patients showed strongly reduced discrimination accuracy, confirming previous work. The behavioral deficits corresponded to pronounced decreases in the evoked EEG response at around 200 ms after stimulus onset. At this latency, patients showed decreased activity for targets in left parietal cortex (dorsal stream), but the decrease was most pronounced in lateral occipital cortex (in the ventral stream). These deficiencies occurred at latencies that reflect object processing and fine shape discriminations. We relate the reduced ventral stream activity to deficient top-down processing of target stimuli and provide a framework for relating the commonly observed dorsal stream deficiencies with the currently observed ventral stream deficiencies.

Non-retinotopic feature integration decreases response-locked brain activity as revealed by electrical neuroimaging

When presented with dynamic scenes, the brain integrates visual elements across space and time. Such non-retinotopic processing has been intensively studied from a psychophysical point of view, but little is known about the underlying neural processes. Here we used high-density EEG to reveal neural correlates of non-retinotopic feature integration. In an offset-discrimination task we presented sequences of lines for which feature integration depended on a small, endogenous shift of attention. Attention effects were observed in the stimulus-locked evoked potentials but non-retinotopic feature integration was reflected in voltage topographies time-locked to the behavioral response, lasting for about 400 ms. Statistical parametric mapping of estimated current densities revealed that this integration reduced electrical activity in an extensive network of brain areas, with the effects progressing from high-level visual, via frontal, to central ones. The results suggest that endogenously timed neural processes, rather than bottom-up ones, underlie non-retinotopic feature integration.

Eye fixation-related potentials in free viewing identify encoding failures in change detection

We considered the hypothesis that spontaneous dissociation between the direction of attention and eye movement causes encoding failure in change detection. We tested this hypothesis by analyzing eye fixation-related potentials (EFRP) at the encoding stage of a change blindness task; when participants freely inspect a scene containing an unmarked target region, in which a change will occur in a subsequent presentation. We measured EFRP amplitude prior to the execution of a saccade, depending on its starting or landing position relative to the target region. For those landings inside the target region, we found a difference in EFRP between correct detection and failure. Overall, correspondence between EFRP amplitude and the size of the saccade predicted successful detection of change; lack of correspondence was followed by change blindness. By contrast, saccade sizes and fixation durations around the target region were unrelated to subsequent change detection. Since correspondence between EFRP and eye movement indicates that overt attention was given to the target region, we concluded that overt attention is needed for successful encoding and that dissociation between eye movement and attention leads to change blindness.

Functional specialization and dynamic resource allocation in visual cortex

We studied the spatiotemporal characteristics of cortical activity in early visual areas and the fusiform gyri (FG) by means of magnetoencephalography (MEG). Subjects performed a visual classification task, in which letters and visually similar pseudoletters were presented in different surrounds and under different task demands. The stimuli appeared in a cued half of the visual field (VF). We observed prestimulus effects on amplitudes in V1 and Cuneus relating to VF and task demands, suggesting a combination of active anticipation and specialized routing of activity in visual processing. Amplitudes in the right FG between 150 and 350 ms after stimulus onset reflected task demands, while those in the left FG between 300 and 400 ms showed selectivity for graphemes. The contrasting stimulus‐evoked effects in the right and left FG show that the former area is sensitive to task demands irrespective of stimulus content, whereas the left FG is sensitive to stimulus content irrespectively of task demand. Hum Brain Mapp, 2010.