A direct neural measure of variable precision representations in visual working memory.

Visual working memory (VWM) is an active representation enabling the manipulation of item information even in the absence of visual input. A common way to investigate VWM is to analyze the performance at later recall. This approach, however, leaves uncertainties about whether the variation of recall performance is attributable to item encoding and maintenance or to the testing of memorized information. Here, we record the contralateral delay activity (CDA), an established electrophysiological measure of item storage and maintenance, in human subjects performing a delayed orientation precision estimation task. This allows us to link the fluctuation of recall precision directly to the process of item encoding and maintenance. We show that for two sequentially encoded orientation items, the CDA amplitude reflects the precision of orientation recall of both items, with higher precision being associated with a larger amplitude. Furthermore, we show that the CDA amplitudes for the items vary independently from each other, suggesting that the precision of memory representations fluctuates independently.NEW & NOTEWORTHY The present work demonstrates for the first time that the contralateral delay activity (CDA), an online electrophysiological measure of the number of representations maintained in memory, is also a reliable measure of the precision of memory representations. Furthermore, we show that the CDA fluctuates independently for individual items held in memory, thereby providing unambiguous direct neurophysiological support for independently fluctuating memory representations.

Unseen food images capture the attention of hungry viewers: Evidence from event-related potentials.

Motivationally relevant visual targets appear to capture visuospatial attention. This capture is evident behaviorally as faster and more accurate responses, and neurally as an enhanced-amplitude of the N2pc - an index of spatial attention allocation, which is observed even when observers are unaware of the target. In the case of reinforcers such as food or substances of dependence, it is likely that the motivational state of craving accompanying deprivation potentiates this capture. The automaticity of such attentional capture by reward-associated stimuli, as well as its possible interaction with craving, is as yet not completely understood, though it is likely a major explanatory factor in motivated behaviors. For the present experiment, participants completed two EEG recording sessions: one just after eating lunch (sated/non-craving), and the other following a minimum 12-h period of fasting (hungry/craving). For both sessions, participants identified food- and clothing-related targets embedded in an object-substitution masking paradigm, which yielded trials of full target visibility, as well as trials for which targets were present but undetected. Although masking equally disrupted visual awareness of both classes of targets as measured behaviorally, a three-way hunger by visibility by target interaction was observed in the neural data, with unseen food targets eliciting an enhanced N2pc. Interestingly, this subliminal attentional capture by food-related items was observed only during the "hungry" session. No such capture was evident under conditions of full visibility. These findings indicate that attentional capture by food-related images, and reflected in enhancements of the N2pc, is spurred by hunger, and that this effect can be viewed as automatic, or independent of explicit awareness of food-relevant target content.

Anatomically constrained tractography facilitates biologically plausible fiber reconstruction of the optic radiation in multiple sclerosis.

Diffusion-weighted magnetic resonance imaging (dMRI) enables the microstructural characterization and reconstruction of white matter pathways in vivo non-invasively. However, dMRI only provides information on the orientation of potential fibers but not on their anatomical plausibility. To that end, recent methodological advances facilitate the effective use of anatomical priors in the process of fiber reconstruction, thus improving the accuracy of the results. Here, we investigated the potential of anatomically constrained tracking (ACT), a modular addition to the tractography software package MRtrix3, to accurately reconstruct the optic radiation, a commonly affected pathway in multiple sclerosis (MS). Diffusion MRI data were acquired from 28 MS patients and 22 age- and sex-matched healthy controls. For each participant, the optic radiation was segmented based on the fiber reconstruction obtained using ACT. When implementing ACT in MS, it proved essential to incorporate lesion maps to avoid incorrect reconstructions due to tissue-type misclassifications in lesional areas. The ACT-based results were compared with those obtained using two commonly used probabilistic fiber tracking procedures, based on FSL (FMRIB Software Library) and MRtrix3 without ACT. All three procedures enabled a reliable localization of the optic radiation in both MS patients and controls. However, for FSL and MRtrix3 without ACT it was necessary to place an additional waypoint halfway between the lateral geniculate nucleus and the primary visual cortex to filter out anatomically implausible tracks. In the case of ACT, the results with and without an additional waypoint were virtually identical, presumably because the employed anatomical constraints already prevented the occurrence of the most implausible tracks. Irrespective of the employed tractography procedure, increased diffusivity and decreased anisotropy were found in the optic radiation of the MS patients compared to the controls.

Neural correlates of multiple object tracking strategies.

Amazingly, human observers can track four independently moving targets. The present study investigated the neural correlates of multiple-object tracking (MOT). Based on previous work we used a modified MOT-task to which subjects exhibited different behaviors. One half of the subjects showed slower RTs and higher error rates with increasing correspondence between tracked items and a probe consisting of 4 highlighted items presented after the tracking. The other half of the subjects had better performance when the probe fully matched the tracked items. Here we sought to investigate the neural representation of the two divergent behavior types. Using multivariate pattern analysis we observed two partly overlapping functional networks associated with the different behaviors. Subjects that responded fast and accurate to full-congruity trials predominantly showed a functional pattern for the full-congruity condition that was very different from patterns associated with any of the partly congruent conditions. This "deviant" pattern was observed in frontal, parietal and extrastriate visual brain areas. In the group of subjects with decreasing performance for increasing target-probe congruity these same regions exhibited a very different functional relationship, in which increasing congruities were associated with linearly changing neural activity patterns. Early low-tier visual areas exclusively exhibited the linear classification pattern while area LO and the primary motor cortex exclusively showed the deviant pattern across all subjects. The coexistence of both networks in groups with different behaviors provides the neural basis for a flexible behavior that can be flexibly adjusted as a function of the strategy employed in the task.

Tactile stimulation and hemispheric asymmetries modulate auditory perception and neural responses in primary auditory cortex.

Although multisensory integration has been an important area of recent research, most studies focused on audiovisual integration. Importantly, however, the combination of audition and touch can guide our behavior as effectively which we studied here using psychophysics and functional magnetic resonance imaging (fMRI). We tested whether task-irrelevant tactile stimuli would enhance auditory detection, and whether hemispheric asymmetries would modulate these audiotactile benefits using lateralized sounds. Spatially aligned task-irrelevant tactile stimuli could occur either synchronously or asynchronously with the sounds. Auditory detection was enhanced by non-informative synchronous and asynchronous tactile stimuli, if presented on the left side. Elevated fMRI-signals to left-sided synchronous bimodal stimulation were found in primary auditory cortex (A1). Adjacent regions (planum temporale, PT) expressed enhanced BOLD-responses for synchronous and asynchronous left-sided bimodal conditions. Additional connectivity analyses seeded in right-hemispheric A1 and PT for both bimodal conditions showed enhanced connectivity with right-hemispheric thalamic, somatosensory and multisensory areas that scaled with subjects' performance. Our results indicate that functional asymmetries interact with audiotactile interplay which can be observed for left-lateralized stimulation in the right hemisphere. There, audiotactile interplay recruits a functional network of unisensory cortices, and the strength of these functional network connections is directly related to subjects' perceptual sensitivity.

Distinct neural correlates of attending speed vs. coherence of motion.

Attention to specific features of moving visual stimuli modulates the activity in human cortical motion sensitive areas. In this study we employed combined event-related electrophysiological, magnetencephalographic (EEG, MEG) and hemodynamic functional magnetic resonance imaging (fMRI) measures of brain activity to investigate the precise time course and the neural correlates of feature-based attention to speed and coherence. Subjects were presented with an aperture of dots randomly moving either slow or fast, at the same time displaying a high or low level of coherence. The task was to attend either the speed or the coherence and press a button upon the high speed or high coherence stimulus respectively. When attention was directed to the speed of motion enhanced neural activity was found in the dorsal visual area V3a and in the IPL, areas previously shown to be specialized for motion processing. In contrast, when attention was directed to the coherence of motion significant hemodynamic activity was observed in the parietal areas fIPS and SPL that are specialized for the processing of complex motion patterns. Concurrent recordings of the event-related electro- and magnetencephalographic responses revealed that the speed-related attentional modulations of activity occurred at an earlier time range (around 240-290 ms), while the coherence-related ones occurred later (around 320-370 ms) post-stimulus. The current results suggest that the attentional selection of motion features modulates neural processing in the lowest-tier regions required to perform the task-critical discrimination.

The center-surround profile of the focus of attention arises from recurrent processing in visual cortex.

We recently demonstrated with magnetoencephalographic recordings in human observers that the focus of attention in visual search has a spatial profile consisting of a center enhancement surrounded by a narrow zone of sensory attenuation. Here, we report new data from 2 experiments providing insights into the cortical processes that cause the surround attenuation. We show that surround suppression appears in search tasks that require spatial scrutiny, that is the precise binding of search-relevant features at the target's location but not in tasks that permit target discrimination without precise localization. Furthermore, we demonstrate that surround attenuation is linked with a stronger recurrent activity modulation in early visual cortex. Finally, we show that surround suppression appears with a delay (more than 175 ms) that is beyond the time course of the initial feedforward sweep of processing in the visual system. These observations together indicate that the suppressive surround is associated with recurrent processing and binding in the visual cortex.

Sensory MEG responses predict successful and failed inhibition in a stop-signal task.

In the present study magnetoencephalographic recordings were performed to investigate the neural mechanisms underlying the stopping of manual responses. Subjects performed in a Stop-signal task in which Go-stimuli (S1), requiring a rapid motor response, were sometimes rapidly followed by a Stop-stimulus (S2) indicating to withhold the already initiated response to S1. Success of stopping strongly depended on the early perceptual processing of S1 and S2 reflected by the magnetic N1 component. Enhanced processing of S1 facilitated the execution of the movement, whereas enhanced processing of S2 favored its inhibition. This suggests that the processing resources for the subsequent stimuli are limited and need to be shared. This sharing of resources appeared to arise from adjustments made on a trial-by-trial basis, in that systematic reaction time prolongations on Go-trials following Stop-trials versus following Go-trials were accompanied by attenuated sensory processing to the Go-stimulus similar to that seen in successful versus unsuccessful stopping in Stop-trials.

Rapid recurrent processing gates awareness in primary visual cortex.

Visual awareness has been proposed to depend on recurrent processing in early visual cortex areas including the primary visual cortex (V1). Here, we address this hypothesis with high spatiotemporal resolution magnetoencephalographic recordings in subjects performing a substitution masking paradigm. Neural activity reflecting awareness is assessed by directly comparing the neuromagnetic response elicited by effectively and ineffectively masked targets after the proportion of trials leading to masking was individually adjusted to match the proportion of trials without masking. This revealed a modulation of recurrent activity in the primary visual cortex rapidly after the onset of the feedforward sweep of processing in striate and extrastriate areas but significantly before the onset of attention-dependent recurrent modulations in V1. Our data provide direct support for the notion that (i) recurrent processing in V1 correlates with visual awareness and (ii) that attention and awareness involve distinct recurrent processing operations.

Spatio-temporal analysis of feature-based attention.

The cortical mechanisms of feature-selective attention to color and motion cues were studied in humans using combined electrophysiological, magnetoencephalographic, and hemodynamic (functional magnetic resonance imaging) measures of brain activity. Subjects viewed a display of random dots that periodically either changed color or moved coherently. When attention was directed to the color change it elicited enhanced neural activity in visual area V4v, previously shown to be specialized for processing color information. In contrast, when dot movement was attended it produced enhanced activity in the motion-specialized area human MT. Parallel recordings of event-related electrophysiological and magnetoencephalographic responses indicated that the attention-related facilitation of neural activity in these specialized cortical areas occurred rapidly, beginning as early as 90-120 ms after stimulus onset. We conclude that selection of an entire feature dimension (motion or color) boosts neural activity in its specialized cortical module much more rapidly than does selection of one feature value from another (e.g., one color from another), as reported in previous electrophysiological studies. By combining methods with high spatial and temporal resolution it is possible to analyze the precise time course of feature-selective processing in specialized cortical areas.

Causal visual interactions as revealed by an information theoretic measure and fMRI.

In the present study, we evaluated the direction of the effective connectivity between fMRI activations in neural structures mediating preserved visual function in a patient with homonymous hemianopsia due to a posterior cerebral artery stroke. Although the lesion affected the primary visual cortex, the visual abilities of this patient included above-chance verbal reports of movement and color change as well as the discrimination of movement direction in his hemianopic field. These abilities were coupled with awareness (Riddoch syndrome). The strength and the direction of the interactions between visual regions were assessed by applying directed transinformation (T), a nonparametric information theoretic causal measure sensitive to linear as well as to nonlinear interactions. In the healthy hemisphere, T identified a strong flow of information from visual area V1 to V5 during stimulation by visual movement and from V1 to V4/V8 during stimulation by color change. In addition, during color change stimulation, a bi-directional flow was observed between V4/V8 and V5, suggesting crosstalk between these regions. In the lesioned hemisphere, the color change stimulation evoked a stronger flow from V5 to V4/V8 and a flow from V4/V8 to V2. These observations provide support for the hypothesis that visual information is mediated via subcortical pathways that bypass V1 and project first to higher-tier visual areas V5 and V4/V8 then subsequently to lower-tier area V2.

Direct neurophysiological evidence for spatial suppression surrounding the focus of attention in vision.

The spatial focus of attention has traditionally been envisioned as a simple spatial gradient of enhanced activity that falls off monotonically with increasing distance. Here, we show with high-density magnetoencephalographic recordings in human observers that the focus of attention is not a simple monotonic gradient but instead contains an excitatory peak surrounded by a narrow inhibitory region. To demonstrate this center-surround profile, we asked subjects to focus attention onto a color pop-out target and then presented probe stimuli at various distances from the target. We observed that the electromagnetic response to the probe was enhanced when the probe was presented at the location of the target, but the probe response was suppressed in a narrow zone surrounding the target and then recovered at more distant locations. Withdrawing attention from the pop-out target by engaging observers in a demanding foveal task eliminated this pattern, confirming a truly attention-driven effect. These results indicate that neural enhancement and suppression coexist in a spatially structured manner that is optimal to attenuate the most deleterious noise during visual object identification.

Functional magnetic resonance tomography correlates of taste perception in the human primary taste cortex.

The present study investigated the functional magnetic resonance tomography correlates of taste perception in the human primary taste cortex. There is conflicting evidence in the literature about chemotopical organization in this brain region. The topography of hemodynamic activity elicited by five taste stimuli (sweet, sour, salty, bitter and umami) was analyzed on the flattened cortical surfaces of six single subjects. A high inter-individual topographical variability had to be noted. The results showed different patterns of hemodynamic activity for the investigated tastes with some considerable overlap. However, the taste specific patterns were stable over time in each subject. Such an individual taste specific pattern was also found for the umami taste within the primary taste cortex of each subject. These results suggest that input from glutamate receptors on the tongue might be processed in an exclusive way in the primary taste cortex rather than as a combination of inputs from the classical taste receptors.

Clinical criteria for the switch of treatment strategies in Parkinson's disease.

Along the years the treatment of Parkinson's disease with L-dopa has revealed unfavorable effects in general after 5-10 years. This has led to the present criteria for treatment of de novo patients that mainly relay on the age, the general strategy being to delay the use of L-dopa as long as possible. However, this practical approach lacks a scientific basis. In a retrospective study data of 155 patients with Parkinson's disease were analyzed with the goal of finding a clinical marker for the critical time point when L-dopa needs to be administrated. The clinical stage of the patients was assessed using the Hoehn and Yahr (H&Y) scale and the severity of the symptoms was measured using the UPDRS score. The results show that there was no relationship between the age of the patients and the therapy (L-dopa vs. no L-dopa) with regard to the clinical outcome. A significant interaction was found however, between the clinical stage (H&Y) and the therapy. Further analysis of this interaction showed that in the H&Y Stages 1-2.5 the UPDRS scores were lower in the patient groups treated without L-dopa. Remarkably, in the H&Y stages 3 and higher the UPDRS scores were lower in the patient groups treated with L-dopa. These results suggest that the clinical stage of the disease (H&Y) might be a better criterion than the age for the time point when L-dopa needs to be administered in de novo patients.

Dynamics of feature binding during object-selective attention.

Objects in the environment may be attended selectively and perceived as unified ensembles of their constituent features. To investigate the timing and cortical localization of feature-integration mechanisms in object-based attention, recordings of event-related potentials and magnetic fields were combined with functional MRI while subjects attended to one of two superimposed transparent surfaces formed by arrays of dots moving in opposite directions. A spatiotemporal analysis revealed evidence for a rapid increase in neural activity localized to a color-selective region of the fusiform gyrus when the surface moving in the attended direction displayed an irrelevant color feature. These data provide support for the "integrated-competition" model of object-selective attention and point to a dynamic neural substrate for the rapid binding process that links relevant and irrelevant features to form a unified perceptual object.

Form-from-motion: MEG evidence for time course and processing sequence.

The neural mechanisms and role of attention in the processing of visual form defined by luminance or motion cues were studied using magnetoencephalography. Subjects viewed bilateral stimuli composed of moving random dots and were instructed to covertly attend to either left or right hemifield stimuli in order to detect designated target stimuli that required a response. To generate form-from-motion (FFMo) stimuli, a subset of the dots could begin to move coherently to create the appearance of a simple form (e.g., square). In other blocks, to generate form-from-luminance (FFLu) stimuli that served as a control, a gray stimulus was presented superimposed on the randomly moving dots. Neuromagnetic responses were observed to both the FFLu and FFMo stimuli and localized to multiple visual cortical stages of analysis. Early activity in low-level visual cortical areas (striate/early extrastriate) did not differ for FFLu versus FFMo stimuli, nor as a function of spatial attention. Longer latency responses elicited by the FFLu stimuli were localized to the ventral-lateral occipital cortex (LO) and the inferior temporal cortex (IT). The FFMo stimuli also generated activity in the LO and IT, but only after first eliciting activity in the lateral occipital cortical region corresponding to MT/V5, resulting in a 50-60 msec delay in activity. All of these late responses (MT/V5, LO, and IT) were significantly modulated by spatial attention, being greatly attenuated for ignored FFLu and FFMo stimuli. These findings argue that processing of form in IT that is defined by motion requires a serial processing of information, first in the motion analysis pathway from V1 to MT/V5 and thereafter via the form analysis stream in the ventral visual pathway to IT.

Unmasking motion-processing activity in human brain area V5/MT+ mediated by pathways that bypass primary visual cortex.

Most models of the human visual system argue that higher-order motion-processing cortical regions receive their inputs only via the primary visual cortex (striate cortex), rather than also via direct projections from the thalamus that bypass primary visual cortex. However, recent evidence in non-human primates, along with some evidence in humans with damaged primary visual cortex (e.g., "blindsight" for motion in the blind visual hemifield), have argued for the existence of a direct thalamic-to-extrastriate projection for motion processing. This evidence remains controversial. Here we tested the idea that direct thalamic input to extrastriate motion processing areas exists in humans but might be masked in scalp recordings by activity from early visual areas. To do this, we employed stimuli that induced strong refractory effects in primary visual cortex--thereby creating a brief "reversable lesion" in primary visual cortex--immediately before the presentation of a motion stimulus. Under these conditions, we then assessed whether motion areas of cortex were still able to process the motion stimuli by recording event-related potentials (ERPs) and event-related magnetic fields (ERFs/MEG). We found robust motion-related activity in extrastriate motion processing areas in the ERP and MEG signals even when primary visual cortex was heavily suppressed by our manipulation. This finding provides evidence for a direct thalamic functional pathway to extrastriate visual cortical motion processing areas in the human that bypasses primary visual cortex.

Amantadine influences cognitive processing in patients with multiple sclerosis.

We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis (MS) and fatigue with objective electrophysiological measures. Behavioral methods (Reaction Time, RT) and two different Event Related Potential (ERP) components measuring i) stimulus selection (Selection Negativity, SN) and ii) response selection (Lateralized Readiness Potential, LRP) were employed. Twenty-four patients with clinical definite MS (10 relapsing remitting and 14 secondary progressive) and confirmed fatigue in the past three months (Fatigue Severity Scale (FSS) > 4) were included. Patients were randomized in a double-blind, placebo-controlled cross-over design. We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms. This negativity had a higher amplitude during amantadine treatment regardless of treatment order. The RT did not differ significantly between the treated and untreated groups. Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position (practice effect), but no treatment effect, while patients with a longer MS duration showed no practice effect, but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine. The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS, but appears to be limited to subjects with a longer duration of the disease.