Recent evidence in healthy participants suggests that a motor subcomponent of working memory (mWM) may exist. We investigated whether this mWM is impaired in patients with a motor-dominant left hemisphere (LH) stroke and apraxia. Furthermore, we hypothesized that a deficient mWM contributes to deficits in motor cognition, that is, apraxia, in LH stroke. The study included 52 patients with LH stroke and 25 age-matched controls. Patients were classified into LH stroke patients with and without apraxia based on deficits in gesture imitation and object use. All participants were examined using the block span test (visuospatial WM), the digit span test (verbal WM), and a novel mWM task. In the latter, participants were presented with static pictures depicting three different actions: actions with objects, meaningless actions, and meaningful actions. In the mWM task, LH stroke patients with apraxia performed worse than age-matched controls. Notably, LH stroke patients with apraxia showed more pronounced mWM deficits than those without apraxia. These results remained significant even after controlling for visuospatial and verbal WM deficits. Regression analyses revealed that LH stroke patients' mWM deficits predicted deficits in imitation. Data provide neuropsychological evidence for a motor subsystem of WM and suggest that deficits in mWM contribute to the severity of apraxia in LH stroke patients.

Although multiple studies characterized the resting-state functional connectivity (rsFC) of the right temporoparietal junction (rTPJ), little is known about the link between rTPJ rsFC and cognitive functions. Given a putative involvement of rTPJ in both reorienting of attention and the updating of probabilistic beliefs, this study characterized the relationship between rsFC of rTPJ with dorsal and ventral attention systems and these two cognitive processes. Twenty-three healthy young participants performed a modified location-cueing paradigm with true and false prior information about the percentage of cue validity to assess belief updating and attentional reorienting. Resting-state fMRI was recorded before and after the task. Seed-based correlation analysis was employed, and correlations of each behavioral parameter with rsFC before the task, as well as with changes in rsFC after the task, were assessed in an ROI-based approach. Weaker rsFC between rTPJ and right intraparietal sulcus before the task was associated with relatively faster updating of the belief that the cue will be valid after false prior information. Moreover, relatively faster belief updating, as well as faster reorienting, were related to an increase in the interhemispheric rsFC between rTPJ and left TPJ after the task. These findings are in line with task-based connectivity studies on related attentional functions and extend results from stroke patients demonstrating the importance of interhemispheric parietal interactions for behavioral performance. The present results not only highlight the essential role of parietal rsFC for attentional functions but also suggest that cognitive processing during a task changes connectivity patterns in a performance-dependent manner.

The processing of congruent stimuli, such as an object or action in its typical location, is usually associated with reduced neural activity, probably due to facilitated recognition. However, in some situations, congruency increases neural activity—for example, when objects next to observed actions are likely versus unlikely to be involved in forthcoming action steps. Here, we investigated using fMRI whether the processing of contextual cues during action perception is driven by their (in)congruency and, thus, informative value to make sense of an observed scene. Specifically, we tested whether both highly congruent contextual objects (COs), which strongly indicate a future action step, and highly incongruent COs, which require updating predictions about possible forthcoming action steps, provide more anticipatory information about the action course than moderately congruent COs. In line with our hypothesis that especially the inferior frontal gyrus (IFG) subserves the integration of the additional information into the predictive model of the action, we found highly congruent and incongruent COs to increase bilateral activity in action observation nodes, that is, the IFG, the occipitotemporal cortex, and the intraparietal sulcus. Intriguingly, BA 47 was significantly stronger engaged for incongruent COs reflecting the updating of prediction in response to conflicting information. Our findings imply that the IFG reflects the informative impact of COs on observed actions by using contextual information to supply and update the currently operating predictive model. In the case of an incongruent CO, this model has to be reconsidered and extended toward a new overarching action goal.

Surprising events may be relevant or irrelevant for behavior, requiring either flexible adjustment or stabilization of our model of the world and according response strategies. Cognitive flexibility and stability in response to environmental demands have been described as separable cognitive states, associated with activity of striatal and lateral prefrontal regions, respectively. It so far remains unclear, however, whether these two states act in an antagonistic fashion and which neural mechanisms mediate the selection of respective responses, on the one hand, and a transition between these states, on the other. In this study, we tested whether the functional dichotomy between striatal and prefrontal activity applies for the separate functions of updating (in response to changes in the environment, i.e., switches) and shielding (in response to chance occurrences of events violating expectations, i.e., drifts) of current predictions. We measured brain activity using fMRI while 20 healthy participants performed a task that required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press while sequence omissions (drifts) had to be ignored. We further varied the probability of switches and drifts to assess the neural network supporting the transition between flexible and stable cognitive states as a function of recent performance history in response to environmental demands. Flexible switching between models was associated with activation in medial pFC (BA 9 and BA 10), whereas stable maintenance of the internal model corresponded to activation in the lateral pFC (BA 6 and inferior frontal gyrus). Our findings extend previous studies on the interplay of flexibility and stability, suggesting that different prefrontal regions are activated by different types of prediction errors, dependent on their behavioral requirements. Furthermore, we found that striatal activation in response to switches and drifts was modulated by participants' successful behavior toward these events, suggesting the striatum to be responsible for response selections following unpredicted stimuli. Finally, we observed that the dopaminergic midbrain modulates the transition between different cognitive states, thresholded by participants' individual performance history in response to temporal environmental demands.

Selective visual attention requires an efficient coordination between top–down and bottom–up attention control mechanisms. This study investigated the behavioral and neural effects of top–down focused spatial attention on the coding of highly salient distractors and their tendency to capture attention. Combining spatial cueing with an irrelevant distractor paradigm revealed bottom–up based attentional capture only when attention was distributed across the whole search display, including the distractor location. Top–down focusing spatial attention on the target location abolished attentional capture of a salient distractor outside the current attentional focus. Functional data indicated that the missing capture effect was not based on diminished bottom–up salience signals at unattended distractor locations. Irrespectively of whether salient distractors occurred at attended or unattended locations, their presence enhanced BOLD signals at their respective spatial representation in early visual areas as well as in inferior frontal, superior parietal, and medial parietal cortex. Importantly, activity in these regions reflected the presence of a salient distractor rather than attentional capture per se. Moreover, successfully inhibiting attentional capture of a salient distractor at an unattended location further increased neural responses in medial parietal regions known to be involved in controlling spatial attentional shifts. Consequently, data provide evidence that top–down focused spatial attention prevents automatic attentional capture by supporting attentional control processes counteracting a spatial bias toward a salient distractor.

During rehabilitation after stroke motor sequence learning is of particular importance because considerable effort is devoted to (re)acquiring lost motor skills. Previous studies suggest that implicit motor sequence learning is preserved in stroke patients but were restricted to the spatial dimension, although the timing of single action components is as important as their spatial order. As the left parietal cortex is known to play a critical role in implicit timing and spatiotemporal integration, in this study we applied an adapted version of the SRT task designed to assess both spatial (different stimulus locations) and temporal (different response–stimulus intervals) aspects of motor learning to 24 right-handed patients with a single left-hemisphere (LH) stroke and 24 age-matched healthy controls. Implicit retrieval of sequence knowledge was tested both at Day 1 and after 24 hr (Day 2). Additionally, voxel-based lesion symptom mapping was used to investigate the neurobiological substrates of the behavioral effects. Although LH stroke patients showed a combined spatiotemporal learning effect that was comparable to that observed in controls, LH stroke patients did not show learning effects for the learning probes in which only one type of sequence information was maintained whereas the other one was randomized. Particularly on Day 2, patients showed significantly smaller learning scores for these two learning probes than controls. Voxel-based lesion symptom mapping analyses revealed for all learning probes that diminished learning scores on Day 2 were associated with lesions of the striatum. This might be attributed to its role in motor chunking and offline consolidation as group differences occurred on Day 2 only. The current results suggest that LH stroke patients rely on multimodal information (here: temporal and spatial information) when retrieving motor sequence knowledge and are very sensitive to any disruption of the learnt sequence information as they seem to build very rigid chunks preventing them from forming independent spatial and temporal sequence representations.

The spatial and temporal context of an object influence its perceived size. Two visual illusions illustrate this nicely: the size adaptation effect and the Ebbinghaus illusion. Whereas size adaptation affects size rescaling of a target circle via a previously presented, differently sized adaptor circle, the Ebbinghaus illusion alters perceived size by virtue of surrounding circles. In the classical Ebbinghaus setting, the surrounding circles are shown simultaneously with the target. However, size underestimation persists when the surrounding circles precede the target. Such a temporal separation of inducer and target circles in both illusions permits the comparison of BOLD signals elicited by two displays that, although objectively identical, elicit different percepts. The current study combined both illusions in a factorial design to identify a presumed common central mechanism involved in rescaling retinal into perceived size. At the behavioral level, combining both illusions did not affect perceived size further. At the neural level, however, this combination induced functional activation beyond that induced by either illusion separately: An underadditive activation pattern was found within left lingual gyrus, right supramarginal gyrus, and right superior parietal cortex. These findings provide direct behavioral and functional evidence for the presence of a neural bottleneck in rescaling retinal into perceived size, a process vital for visual perception.

A moon near to the horizon is perceived larger than a moon at the zenith, although—obviously—the moon does not change its size. In this study, the neural mechanisms underlying the “moon illusion” were investigated using a virtual 3-D environment and fMRI. Illusory perception of an increased moon size was associated with increased neural activity in ventral visual pathway areas including the lingual and fusiform gyri. The functional role of these areas was further explored in a second experiment. Left V3v was found to be involved in integrating retinal size and distance information, thus indicating that the brain regions that dynamically integrate retinal size and distance play a key role in generating the moon illusion.

On the basis of double dissociations in clinical symptoms of patients with unilateral visuospatial neglect, neuropsychological research distinguishes between different spatial domains (near vs. far) and different spatial reference frames (egocentric vs. allocentric). In this fMRI study, we investigated the neural interaction between spatial domains and spatial reference frames by constructing a virtual three-dimensional world and asking participants to perform either allocentric or egocentric judgments on an object located in either near or far space. Our results suggest that the parietal–occipital junction (POJ) not only shows a preference for near-space processing but is also involved in the neural interaction between spatial domains and spatial reference frames. Two dissociable streams of visual processing exist in the human brain: a ventral perception-related stream and a dorsal action-related stream. Consistent with the perception–action model, both far-space processing and allocentric judgments draw upon the ventral stream whereas both near-space processing and egocentric judgments draw upon the dorsal stream. POJ showed higher neural activity during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral) as compared with egocentric judgments (dorsal) in near space (dorsal) and allocentric judgments (ventral) in far space (ventral). Because representations in the dorsal and ventral streams need to interact during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral), our results imply that POJ is involved in the neural interaction between the two streams. Further evidence for the suggested role of POJ as a neural interface between the dorsal and ventral streams is provided by functional connectivity analysis.

The human visual system converts identically sized retinal stimuli into different-sized perceptions. For instance, the Müller-Lyer illusion alters the perceived length of a line via arrows attached to its end. The strength of this illusion can be expressed as the difference between physical and perceived line length. Accordingly, illusion strength reflects how strong a representation is transformed along its way from a retinal image up to a conscious percept. In this study, we investigated changes of effective connectivity between brain areas supporting these transformation processes to further elucidate the neural underpinnings of optical illusions. The strength of the Müller-Lyer illusion was parametrically modulated while participants performed either a spatial or a luminance task. Lateral occipital cortex and right superior parietal cortex were found to be associated with illusion strength. Dynamic causal modeling was employed to investigate putative interactions between ventral and dorsal visual streams. Bayesian model selection indicated that a model that involved bidirectional connections between dorsal and ventral stream areas most accurately accounted for the underlying network dynamics. Connections within this network were partially modulated by illusion strength. The data further suggest that the two areas subserve differential roles: Whereas lateral occipital cortex seems to be directly related to size transformation processes, activation in right superior parietal cortex may reflect subsequent levels of processing, including task-related supervisory functions. Furthermore, the data demonstrate that the observer's top–down settings modulate the interactions between lateral occipital and superior parietal regions and thereby influence the effect of illusion strength.

In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532–1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging.

Older individuals show decline of prefrontal cortex (PFC) functions which may be related to altered dopaminergic neurotransmission. We investigated the effects of aging and dopaminergic stimulation in 15 young and 13 older healthy subjects on the neural correlates of interference control using fMRI. In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration. In each session, subjects performed a visual–spatial interference task based on a Stroop/Simon-like paradigm. Across age groups, interference (incongruent relative to congruent trials) was associated with activations in the presupplementary motor area, ACC, and intraparietal cortex. Increased interference was found behaviorally in older volunteers. Differential activation in left dorsolateral PFC in young subjects and bilateral PFC activity in older subjects was observed to be associated with interference control. Performance deteriorated under levodopa only in young subjects. This was accompanied by an increase of neural activity in ACC ( p < .05; small-volume correction for multiple comparisons). Worsening of performance under levodopa in young subjects and the associated effect on ACC may indicate that overstimulation of the dopaminergic system compromises interference control. This supports the inverted-U-shaped model of neurotransmitter action.

Besides the fact that RTs in cognitive tasks are affected by the specific demands of a trial, the context in which this trial occurs codetermines the speed of the response. For instance, invalid spatial cues generally prolong RTs to targets in the location-cueing paradigm, whereas the magnitude of these RT costs additionally varies as a function of the preceding trial types so that RTs for invalid trials may be increased when preceded by valid rather than invalid trials. In the present fMRI study, we investigated trial sequence effects in a combined oddball and location-cueing paradigm. In particular, we tested whether RTs and neural activity to infrequent invalid or deviant targets varied as a function of the number of preceding valid standard trials. As expected, RTs in invalid and deviant trials were significantly slower when more valid standard trials had been presented beforehand. This behavioral effect was reflected in the neural activity of the right inferior/middle frontal gyrus where the amplitude of the hemodynamic response in invalid and deviant trials was positively related to the number of preceding valid standard trials. In contrast, decreased activity (i.e., a negative parametric modulation effect) was observed when more valid standard trials were successively presented. Further positive parametric effects for the number of preceding valid standard trials were observed in the left caudate nucleus and lingual gyrus. The data suggest that inferior frontal cortex extracts both event regularities and irregularities in event streams.

The ability and motivation to share attention is a unique aspect of human cognition. Despite its significance, the neural basis remains elusive. To investigate the neural correlates of joint attention , we developed a novel, interactive research paradigm in which participants' gaze behavior—as measured by an eye tracking device—was used to contingently control the gaze of a computer-animated character. Instructed that the character on screen was controlled by a real person outside the scanner, 21 participants interacted with the virtual other while undergoing fMRI. Experimental variations focused on leading versus following the gaze of the character when fixating one of three objects also shown on the screen. In concordance with our hypotheses, results demonstrate, firstly, that following someone else's gaze to engage in joint attention resulted in activation of anterior portion of medial prefrontal cortex (MPFC) known to be involved in the supramodal coordination of perceptual and cognitive processes. Secondly, directing someone else's gaze toward an object activated the ventral striatum which—in light of ratings obtained from participants—appears to underlie the hedonic aspects of sharing attention. The data, therefore, support the idea that other-initiated joint attention relies upon recruitment of MPFC previously related to the “meeting of minds.” In contrast, self-initiated joint attention leads to a differential increase of neural activity in reward-related brain areas, which might contribute to the uniquely human motivation to engage in the sharing of experiences.

Endogenous control of visual search can influence search guidance at the level of a supradimensional topographic saliency map [Wolfe, J. M. Guided Search 2.0: A revised model of visual search. Psychonomic Bulletin & Review, 1, 202–238, 1994], and modulate nonspatial mechanisms coding saliency in dimension-specific input modules [Müller, H. J., Reimann, B., & Krummenacher, J. Visual search for singleton feature targets across dimensions: Stimulus- and expectancy-driven effects in dimensional weighting. Journal of Experimental Psychology: Human Perception and Performance, 29, 1021–1035, 2003]. The current experiment used fMRI to dissociate these mechanisms in a singleton feature search task in which the likely target dimension (color or orientation) was semantically precued and target saliency in each dimension was varied parametrically. BOLD signal increases associated with increased demands for top–down guidance were observed within the fronto-parietal attention network and in the right anterior middle frontal gyrus. Decreasing requirements for top–down control led to BOLD signal increases in medial anterior prefrontal cortex, consistent with a gating mechanism in favor of stimulus-related processing [Burgess, P. W., Dumontheil, I., & Gilbert, S. J. The gateway hypothesis of rostral prefrontal cortex (area 10) function. Trends in Cognitive Sciences, 11, 290–298, 2007]. Another network of brain areas consisting of left lateral fronto-polar cortex, the left supramarginal gyrus, and the cerebellum, as well as a bilateral network consisting of the posterior orbital gyrus, the inferior frontal gyrus, and the pre-SMA were associated with top–down dimensional (re-) orienting. These data argue in favor of distinct endogenous control systems for visuospatial and dimension-based attentional processing. Finally, cue validity modulated saliency processing in the left temporo-parietal junction (TPJ), pointing to a crucial role of the left TPJ in integrating an endogenous dimension-based attention set with bottom–up saliency signals.

In synesthesia, stimulation of one sensory modality leads to a percept in another nonstimulated modality, for example, graphemes trigger an additional color percept in grapheme–color synesthesia, which encompasses the variants letter–color and digit–color synesthesia. Until recently, it was assumed that synesthesia occurs strictly unidirectional: Although the perception of a letter induces a color percept in letter–color synesthetes, they typically do not report that colors trigger the percept of a letter. Recent data on number processing in synesthesia suggest, however, that colors can implicitly elicit numerical representations in digit–color synesthetes, thereby questioning unidirectional models of synesthesia. Using a word fragment completion paradigm in 10 letter–color synesthetes, we show here for the first time that colors can implicitly influence lexical search. Our data provide strong support for a bidirectional nature of grapheme–color synesthesia and, in general, may allude to the mechanisms of cross-modality interactions in the human brain.

Action understanding and learning are suggested to be mediated, at least in part, by the human mirror neuron system (hMNS). Static images as well as videos of actions with the outcome occluded have been shown to activate the hMNS. However, whether the hMNS preferentially responds to end or means of an action remains to be investigated. We, therefore, presented subjects with videos of intentional actions that were shown from two perspectives (factor 1, perspective: first vs. third person) while subjects directed their attention to the means or the end thereof (factor 2, task: means vs. end). End- or means-related changes in BOLD signal and corticospinal excitability (CSE) were assessed using fMRI and TMS, respectively. Judging the means of an action compared with its end differentially activated bilateral ventral premotor (vPMC) and inferior parietal cortex (IPL), that is, the core regions of the hMNS. The reverse contrast revealed left precuneus and bilateral superior frontal, angular, and middle temporal gyrus activity. In accordance, the two tasks, although identically in stimulus properties, modulated CSE differentially. Although recent studies suggest that the hMNS may prefer the presence of a goal or context, our data show that within the same context, it responds preferentially when attention is directed to the action means . Consequently, in addition to inferring action goals, a key function of the hMNS may be to anticipate the trajectories and dynamics of observed actions, which is a prerequisite for any timely interaction.

Within the parietal cortex, the temporo-parietal junction (TPJ) and the intraparietal sulcus (IPS) seem to be involved in both spatial and nonspatial functions: Both areas are activated when misleading information is provided by invalid spatial cues in Posner's location-cueing paradigm, but also when infrequent deviant stimuli are presented within a series of standard events. In the present study, we used functional magnetic resonance imaging to investigate the distinct and shared brain responses to (i) invalidly cued targets requiring attentional reorienting, and (ii) to target stimuli deviating in color and orientation leading to an oddball-like distraction effect. Both unexpected location and feature changes were accompanied by a significant slowing of manual reaction times. Bilateral TPJ and right superior parietal lobe (SPL) activation was observed in response to invalidly as compared to validly cued targets. In contrast, the bilateral inferior occipito-temporal cortex, the left inferior parietal cortex, right frontal areas, and the cerebellum showed stronger activation in response to deviant than to standard targets. Common activations were observed in the right angular gyrus along the IPS and in the right inferior frontal gyrus. We conclude that the superior parietal and temporo-parietal activations observed here as well as previously in location-cueing paradigms do not merely reflect the detection and processing of unexpected stimuli. Furthermore, our data suggest that the right IPS and the inferior frontal gyrus are involved in attentional selection and distractor processing of both spatial and nonspatial features.

Attending to a visual stimulus feature, such as color or motion, enhances the processing of that feature in the visual cortex. Moreover, the processing of the attended object's other, unattended, features is also enhanced. Here, we used functional magnetic resonance imaging to show that attentional modulation in the auditory system may also exhibit such feature- and object-specific effects. Specifically, we found that attending to auditory motion increases activity in nonprimary motion-sensitive areas of the auditory cortical “where” pathway. Moreover, activity in these motion-sensitive areas was also increased when attention was directed to a moving rather than a stationary sound object, even when motion was not the attended feature. An analysis of effective connectivity revealed that the motion-specific attentional modulation was brought about by an increase in connectivity between the primary auditory cortex and nonprimary motion-sensitive areas, which, in turn, may have been mediated by the paracingulate cortex in the frontal lobe. The current results indicate that auditory attention can select both objects and features. The finding of feature-based attentional modulation implies that attending to one feature of a sound object does not necessarily entail an exhaustive processing of the object's unattended features.

Empathy allows emotional psychological inference about other person's mental states and feelings in social contexts. We aimed at specifying the common and differential neural mechanisms of “self”- and “other”-related attribution of emotional states using event-related functional magnetic resonance imaging. Subjects viewed faces expressing emotions with direct or averted gaze and either focused on their own emotional response to each face (self-task) or evaluated the emotional state expressed by the face (other-task). The common network activated by both tasks included the left lateral orbito-frontal and medial prefrontal cortices (MPFC), bilateral inferior frontal cortices, superior temporal sulci and temporal poles, as well as the right cerebellum. In a subset of these regions, neural activity was significantly correlated with empathic abilities. The self- (relative to the other-) task differentially activated the MPFC, the posterior cingulate cortex (PCC)/precuneus, and the temporo-parietal junction bilaterally. Empathy-related processing of emotional facial expressions recruited brain areas involved in mirror neuron and theory-of-mind (ToM) mechanisms. The differential engagement of the MPFC, the PCC/precuneus, and temporo-parietal regions in the self-task indicates that these structures act as key players in the evaluation of one's own emotional state during empathic face-to-face interaction. Activation of mirror neurons in a task relying on empathic abilities without explicit task-related motor components supports the view that mirror neurons are not only involved in motor cognition but also in emotional interpersonal cognition. An interplay between ToM and mirror neuron mechanisms may hold for the maintenance of a self-other distinction during empathic interpersonal face-to-face interactions.