Dysfunction of the Human Mirror Neuron System in Ideomotor Apraxia: Evidence from Mu Suppression.

Stroke patients with ideomotor apraxia (IMA) have difficulties controlling voluntary motor actions, as clearly seen when asked to imitate simple gestures performed by the examiner. Despite extensive research, the neurophysiological mechanisms underlying failure to imitate gestures in IMA remain controversial. The aim of the current study was to explore the relationship between imitation failure in IMA and mirror neuron system (MNS) functioning. Mirror neurons were found to play a crucial role in movement imitation and in imitation-based motor learning. Their recruitment during movement observation and execution is signaled in EEG recordings by suppression of the lower (8-10 Hz) mu range. We examined the modulation of EEG in this range in stroke patients with left (n = 21) and right (n = 15) hemisphere damage during observation of video clips showing different manual movements. IMA severity was assessed by the DeRenzi standardized diagnostic test. Results showed that failure to imitate observed manual movements correlated with diminished mu suppression in patients with damage to the right inferior parietal lobule and in patients with damage to the right inferior frontal gyrus pars opercularis-areas where major components of the human MNS are assumed to reside. Voxel-based lesion symptom mapping revealed a significant impact on imitation capacity for the left inferior and superior parietal lobules and the left post central gyrus. Both left and right hemisphere damages were associated with imitation failure typical of IMA, yet a clear demonstration of relationship to the MNS was obtained only in the right hemisphere damage group. Suppression of the 8-10 Hz range was stronger in central compared with occipital sites, pointing to a dominant implication of mu rather than alpha rhythms. However, the suppression correlated with De Renzi's apraxia test scores not only in central but also in occipital sites, suggesting a multifactorial mechanism for IMA, with a possible impact for deranged visual attention (alpha suppression) beyond the effect of MNS damage (mu suppression).

Rehearsing biological motion in working memory: an EEG study.

Holding biological motion (BM), the movements of animate entities, in working memory (WM) is important to our daily social life. However, how BM is maintained in WM remains unknown. The current study investigated this issue and hypothesized that, analogous to BM perception, the human mirror neuron system (MNS) is involved in rehearsing BM in WM. To examine the MNS hypothesis of BM rehearsal, we used an EEG index of mu suppression (8-12 Hz), which has been linked to the MNS. Using a change detection task, we manipulated the BM memory load in three experiments. We predicted that mu suppression in the maintenance phase of WM would be modulated by the BM memory load; moreover, a negative correlation between the number of BM stimuli in WM and the degree of mu suppression may emerge. The results of Experiment 1 were in line with our predictions and revealed that mu suppression increased as the memory load increased from two to four BM stimuli; however, mu suppression then plateaued, as WM could only hold, at most, four BM stimuli. Moreover, the predicted negative correlation was observed. Corroborating the findings of Experiment 1, Experiment 2 further demonstrated that once participants used verbal codes to process the motion information, the mu suppression or modulation by memory load vanished. Finally, Experiment 3 demonstrated that the findings in Experiment 1 were not limited to one specific type of stimuli. Together, these results provide evidence that the MNS underlies the process of rehearsing BM in WM.

Training-induced recovery of low-level vision followed by mid-level perceptual improvements in developmental object and face agnosia.

Long-term deprivation of normal visual inputs can cause perceptual impairments at various levels of visual function, from basic visual acuity deficits, through mid-level deficits such as contour integration and motion coherence, to high-level face and object agnosia. Yet it is unclear whether training during adulthood, at a post-developmental stage of the adult visual system, can overcome such developmental impairments. Here, we visually trained LG, a developmental object and face agnosic individual. Prior to training, at the age of 20, LG's basic and mid-level visual functions such as visual acuity, crowding effects, and contour integration were underdeveloped relative to normal adult vision, corresponding to or poorer than those of 5-6 year olds (Gilaie-Dotan, Perry, Bonneh, Malach & Bentin, 2009). Intensive visual training, based on lateral interactions, was applied for a period of 9 months. LG's directly trained but also untrained visual functions such as visual acuity, crowding, binocular stereopsis and also mid-level contour integration improved significantly and reached near-age-level performance, with long-term (over 4 years) persistence. Moreover, mid-level functions that were tested post-training were found to be normal in LG. Some possible subtle improvement was observed in LG's higher-order visual functions such as object recognition and part integration, while LG's face perception skills have not improved thus far. These results suggest that corrective training at a post-developmental stage, even in the adult visual system, can prove effective, and its enduring effects are the basis for a revival of a developmental cascade that can lead to reduced perceptual impairments.

Mirror-neuron system recruitment by action observation: effects of focal brain damage on mu suppression.

Mu suppression is the attenuation of EEG power in the alpha frequency range (8-12 Hz), recorded over the sensorimotor cortex during execution and observation of motor actions. Based on this dual characteristic mu suppression is thought to signalize activation of a human analogue of the mirror neuron system (MNS) found in macaque monkeys. However, much uncertainty remains concerning its specificity and full significance. To further explore the hypothesized relationship between mu suppression and MNS activation, we investigated how it is affected by damage to cortical regions, including areas where the MNS is thought to reside. EEG was recorded in 33 first-event stroke patients during observation of video clips showing reaching and grasping hand movements. We examined the modulation of EEG oscillations at central and occipital sites, and analyzed separately the lower (8-10 Hz) and higher (10-12 Hz) segments of the alpha/mu range. Suppression was determined relative to observation of a non-biological movement. Normalized lesion data were used to investigate how damage to regions of the fronto-parietal cortex affects the pattern of suppression. The magnitude of mu suppression during action observation was significantly reduced in the affected hemisphere compared to the unaffected hemisphere. Differences between the hemispheres were significant at central (sensorimotor) sites but not at occipital (visual) sites. Total hemispheric volume loss did not correlate with mu suppression. Suppression in the lower mu range in the unaffected hemisphere (C3) correlated with lesion extent within the right inferior parietal cortex. Our lesion study supports the role of mu suppression as a marker of MNS activation, confirming previous studies in normal subjects.

Mapping the time course of other-race face classification advantage: a cross-race ERP study.

The current study investigated the time course of the other-race advantage (ORA) in the subordinate classification of faces by race. A significant ORA was found on RTs for both races. The ERP data showed that the categorization processes follow basic level classification of physiognomic stimuli, which is not influenced by the stimulus race. The most conspicuous difference between own-race and other-race faces was found in the modulation of the amplitude of the P3. Since the amplitude of the P3 is sensitive primarily to the perceptual demands of a task, these data suggest that the delay of the own-race classification is caused by an own-race specific process that precedes or interferes with the subordinate classification.

Resting state functional connectivity reflects abnormal task-activated patterns in a developmental object agnosic.

Even in the absence of stimulation or task, the cerebral cortex shows an incessant pattern of ultra slow fluctuations which are coherent across brain regions. In the healthy brain these coherent patterns (also termed resting state functional connectivity) often exhibit spatial similarity to the large scale organization of task-induced functional networks. However, it is not clear to what extent the resting state patterns can also reflect task-induced abnormalities in cortical activations which are often detected in various brain pathologies. Here we examined whether an abnormal visual activation pattern is recapitulated in the resting state functional connectivity. We examined LG, a sighted young adult with developmental object agnosia and no apparent cortical structural abnormality. We have previously reported that upon visual stimulation, LG's intermediate visual areas (V2, V3) are paradoxically deactivated. Here, examining LG's resting state functional connectivity revealed the same pattern of functional abnormality - including a strong atypical decorrelation between areas V2-V3 and the rest of the visual system. Thus, our results suggest that resting-state functional connectivity could provide a powerful tool which could complement task-specific paradigms in detecting task-related abnormalities in cortical activity without resorting to task performance.

A magnetoencephalographic study of face processing: M170, gamma-band oscillations and source localization.

EEG studies suggested that the N170 ERP and Gamma-band responses to faces reflect early and later stages of a multiple-level face-perception mechanism, respectively. However, these conclusions should be considered cautiously because EEG-recorded Gamma may be contaminated by noncephalic activity such as microsaccades. Moreover, EEG studies of Gamma cannot easily reveal its intracranial sources. Here we recorded MEG rather than EEG, assessed the sources of the M170 and Gamma oscillations using beamformer, and explored the sensitivity of these neural manifestations to global, featural and configural information in faces. The M170 was larger in response to faces and face components than in response to watches. Scrambling the configuration of the inner components of the face even if presented without the face contour reduced and delayed the M170. The amplitude of MEG Gamma oscillations (30-70 Hz) was higher than baseline during an epoch between 230-570 ms from stimulus onset and was particularly sensitive to the configuration of the stimuli, regardless of their category. However, in the lower part of this frequency range (30-40 Hz) only physiognomic stimuli elevated the MEG above baseline. Both the M170 and Gamma were generated in a posterior-ventral network including the fusiform, inferior-occipital and lingual gyri, all in the right hemisphere. The generation of Gamma involved additional sources in the visual system, bilaterally. We suggest that the evoked M170 manifests a face-perception mechanism based on the global characteristics of face, whereas the induced Gamma oscillations are associated with the integration of visual input into a pre-existent coherent perceptual representation.

Neuroanatomical correlates of visual car expertise.

Expertise in non-visual domains such as musical performance is associated with differences in gray matter volume of particular regions of the human brain. Whether this is also the case for expertise in visual object recognition is unknown. Here we tested whether individual variability in the ability to recognize car models, from novice performance to high level of expertise, is associated with specific structural changes in gray matter volume. We found that inter-individual variability in expertise with cars was significantly and selectively correlated with gray matter volume in prefrontal cortex. Inter-individual differences in the recognition of airplanes, that none of the participants had expertise with, were correlated with structural variability of regions bordering the visual cortex. These results highlight the role of prefrontal regions outside the visual cortex in accessing and processing visual knowledge about objects from the domain of expertise and suggest that expertise in visual object recognition may entail structural changes in regions associated with semantic knowledge.

Motor and attentional mechanisms involved in social interaction--evidence from mu and alpha EEG suppression.

Mu rhythms are EEG oscillations in the 8-13 Hz recorded at sites located roughly over the sensory-motor cortex. There is reliable evidence that the amplitude of mu rhythms is reduced when the participant performs a motor act (mu suppression). Recent studies found mu suppression not only in response to actual movements but also while the participant observes actions executed by someone else. This finding putatively associates the mu suppression to the activity of a mirror neurons system which, in humans, has been suggested to contribute to social skills. In the present study we explored the effects of different levels of social interaction on mu suppression. Participants observed dynamic displays of hand gestures performing actions used in the Rock-Scissors-Paper game. In different blocks, participants passively viewed identical video clips with no game context and in the context of a game, or while being actually engaged in the game either by imagining actions or by actual playing. As a baseline for calculating mu suppression we used a dynamic display of a rolling ball. In addition, to isolate the social aspect of the actual movements, participants performed the same acts outside the game context. Mu suppression was larger while participants were engaged in the social game than when they passively looked at the "opponent" actions or when they performed movements without the game context. This effect was found while viewing the opponent play as well as while actually playing, which supports the view that mu suppression is affected not only by motion, but also by the social context of the motion. However, we did not find differences in mu suppression between perception segments in which the participant did not actually play. Furthermore, in all perception segments occipital alpha suppression was more robust than mu suppression suggesting the involvement of a strong attentional component. While actually playing, however, mu suppression was stronger than alpha suppression.

Neural adaptation is related to face repetition irrespective of identity: a reappraisal of the N170 effect.

Event-related potentials offer evidence for face distinctive neural activity that peaks at about 170 ms following the onset of face stimuli (the N170 effect). We investigated the role of the perceptual mechanism reflected by the N170 effect by comparing the adaptation of the N170 amplitude when target faces were preceded either by identical face images or by different faces relative to when they were preceded by objects. In two experiments, we demonstrate that the N170 is equally adapted by repetition of the same or different faces. Thus, our findings show that the N170 is sensitive to the category rather than the identity of a face. This outcome supports the hypothesis that the N170 effect reflects the activity of a perceptual mechanism which discriminates faces from objects and streams face stimuli to dedicated circuits, specialized in encoding and decoding information about the face.

Top-down engagement modulates the neural expressions of visual expertise.

Perceptual expertise is traditionally associated with enhanced brain activity in response to objects of expertise in category-selective visual cortex, primarily face-selective regions. We reevaluated this view by investigating whether the brain activity associated with expertise in object recognition is limited to category-selective cortex and specifically whether the extent of expertise-related activity manifests automatically or whether it can be top-down modulated. We conducted 2 functional magnetic resonance imaging studies comparing changes in hemodynamic activity associated with car expertise in a conventional 1-back task (Experiment 1) and when the task relevance of cars was explicitly manipulated (Experiment 2). Whole-brain analysis unveiled extensive expertise-related activity throughout the visual cortex, starting as early as V1 and extending into nonvisual areas. However, when the cars were task irrelevant, the expertise-related activity drastically diminished, indeed, becoming similar to the activity elicited by cars in novices. We suggest that expertise entails voluntary top-down engagement of multiple neural networks in addition to stimulus-driven activation associated with perceptual mechanisms.

Conscious awareness is necessary for processing race and gender information from faces.

Previous studies suggested that emotions can be correctly interpreted from facial expressions in the absence of conscious awareness of the face. Our goal was to explore whether subordinate information about a face's gender and race could also become available without awareness of the face. Participants classified the race or the gender of unfamiliar faces that were ambiguous with regard to these dimensions. The ambiguous faces were preceded by face-images that unequivocally represented gender and race, rendered consciously invisible by simultaneous continuous-flash-suppression. The classification of ambiguous faces was biased away from the category of the adaptor only when it was consciously visible. The duration of subjective visibility correlated with the aftereffect strength. Moreover, face identity was consequential only if consciously perceived. These results suggest that while conscious awareness is not needed for basic level categorization, it is needed for subordinate categorization. Emotional information might be unique in this respect.

Attentional selection of relative SF mediates global versus local processing: evidence from EEG.

Previous research on functional hemispheric differences in visual processing has associated global perception with low spatial frequency (LSF) processing biases of the right hemisphere (RH) and local perception with high spatial frequency (HSF) processing biases of the left hemisphere (LH). The Double Filtering by Frequency (DFF) theory expanded this hypothesis by proposing that visual attention selects and is directed to relatively LSFs by the RH and relatively HSFs by the LH, suggesting a direct causal relationship between SF selection and global versus local perception. We tested this idea in the current experiment by comparing activity in the EEG recorded at posterior right and posterior left hemisphere sites while participants' attention was directed to global or local levels of processing after selection of relatively LSFs versus HSFs in a previous stimulus. Hemispheric asymmetry in the alpha band (8-12 Hz) during preparation for global versus local processing was modulated by the selected SF. In contrast, preparatory activity associated with selection of SF was not modulated by the previously attended level (global/local). These results support the DFF theory that top-down attentional selection of SF mediates global and local processing.

Basic-level categorization of intermediate complexity fragments reveals top-down effects of expertise in visual perception.

Visual expertise is usually defined as the superior ability to distinguish between exemplars of a homogeneous category. Here, we ask how real-world expertise manifests at basic-level categorization and assess the contribution of stimulus-driven and top-down knowledge-based factors to this manifestation. Car experts and novices categorized computer-selected image fragments of cars, airplanes, and faces. Within each category, the fragments varied in their mutual information (MI), an objective quantifiable measure of feature diagnosticity. Categorization of face and airplane fragments was similar within and between groups, showing better performance with increasing MI levels. Novices categorized car fragments more slowly than face and airplane fragments, while experts categorized car fragments as fast as face and airplane fragments. The experts' advantage with car fragments was similar across MI levels, with similar functions relating RT with MI level for both groups. Accuracy was equal between groups for cars as well as faces and airplanes, but experts' response criteria were biased toward cars. These findings suggest that expertise does not entail only specific perceptual strategies. Rather, at the basic level, expertise manifests as a general processing advantage arguably involving application of top-down mechanisms, such as knowledge and attention, which helps experts to distinguish between object categories.

Neural dynamics associated with semantic and episodic memory for faces: evidence from multiple frequency bands.

Prior semantic knowledge facilitates episodic recognition memory for faces. To examine the neural manifestation of the interplay between semantic and episodic memory, we investigated neuroelectric dynamics during the creation (study) and the retrieval (test) of episodic memories for famous and nonfamous faces. Episodic memory effects were evident in several EEG frequency bands: theta (4-8 Hz), alpha (9-13 Hz), and gamma (40-100 Hz). Activity in these bands was differentially modulated by preexisting semantic knowledge and by episodic memory, implicating their different functional roles in memory. More specifically, theta activity and alpha suppression were larger for old compared to new faces at test regardless of fame, but were both larger for famous faces during study. This pattern of selective semantic effects suggests that the theta and alpha responses, which are primarily associated with episodic memory, reflect utilization of semantic information only when it is beneficial for task performance. In contrast, gamma activity decreased between the first (study) and second (test) presentation of a face, but overall was larger for famous than nonfamous faces. Hence, the gamma rhythm seems to be primarily related to activation of preexisting neural representations that may contribute to the formation of new episodic traces. Taken together, these data provide new insights into the complex interaction between semantic and episodic memory for faces and the neural dynamics associated with mnemonic processes.

"Feeling" the pain of those who are different from us: Modulation of EEG in the mu/alpha range.

We explored how apparently painful stimuli and the ability to identify with the person on whom the pain is inflicted modulate EEG suppression in the mu/alpha range (8-12 Hz). In a 2 × 2 design, we presented pictures of hands either experiencing needle pricks or being touched by a Q-tip. In the dissimilar-other condition, the hand was assigned to a patient suffering from a neurological disease in which Q-tips inflicted pain, whereas needle pricks did not. In the similar-other condition, the hand was assigned to a patient who responded to stimulation in the same way as the healthy participant. Participants were instructed to imagine the feeling of the person whose hand was shown and to evaluate his or her affective state. Pain conditions elicited greater EEG suppression than did nonpain conditions, particularly over frontocentral regions. Moreover, an interaction between pain and similarity revealed that for similar others, the pain effect was significant, whereas in the dissimilar-other group, suppression was equally large in the pain and no-pain conditions. We conclude that mu/alpha suppression is elicited both automatically, by observing a situation that is potentially painful for the observer, and by empathy for pain, even if the other person is different from oneself.

Local or global? Attentional selection of spatial frequencies binds shapes to hierarchical levels.

Contrary to the traditional view that shapes and their hierarchical level (local or global) are a priori integrated in perception, recent evidence suggests that the identity of a shape and its level are encoded independently, implying the need for shape-level binding to account for normal perception. What is the binding mechanism in this case? Using hierarchically arranged letter shapes, we obtained evidence that the left hemisphere has a preference for binding shapes to the local level, whereas the right hemisphere has a preference for binding shapes to the global level. More important, binding is modulated by attentional selection of higher or lower spatial frequencies. Attention to higher spatial frequencies facilitated subsequent binding by the left hemisphere of elements to the local level, whereas attention to lower spatial frequencies facilitated subsequent binding by the right hemisphere of elements to the global level.

Not on the face alone: perception of contextualized face expressions in Huntington's disease.

Numerous studies have demonstrated that Huntington's disease mutation-carriers have deficient explicit recognition of isolated facial expressions. There are no studies, however, which have investigated the recognition of facial expressions embedded within an emotional body and scene context. Real life facial expressions are typically embedded in contexts which may dramatically change the emotion recognized in the face. Moreover, a recent study showed that the magnitude of the contextual bias is modulated by the similarity between the actual expression of the presented face and the facial expression that would typically fit the context, e.g. disgust faces are more similar to anger than to sadness faces and, consequently, are more strongly influenced by contexts expressing anger than by contexts expressing sadness. Since context effects on facial expression perception are not explicitly controlled, their pattern serves as an implicit measure of the processing of facial expressions. In this study we took advantage of the face-in-context design to compare explicit recognition of face-expressions by Huntington's disease mutation-carriers, with evidence for processing the expressions deriving from implicit measures. In an initial experiment we presented a group of 21 Huntington's disease mutation-carriers with standard tests of face-expression recognition. Relative to controls, they displayed deficits in recognizing disgust and anger faces despite intact recognition of these emotions from non-facial images. In a subsequent experiment, we embedded the disgust faces on images of people conveying sadness and anger as expressed by body language and additional paraphernalia. In addition, sadness and anger faces were embedded on context images conveying disgust. In both cases participants were instructed to categorize the facial expressions, ignoring the context. Despite the deficient explicit recognition of isolated disgust and anger faces, the perception of the emotions expressed by the faces was affected by context in Huntington's disease mutation-carriers in a similar manner as in control participants. Specifically, they displayed the same sensitivity to face-context pairings. These findings suggest that, despite their impaired explicit recognition of facial expressions, Huntington's disease mutation-carriers display relatively preserved processing of the same facial configurations when embedded in context. The results also show intact utilization of the information elicited by contextual cues about faces expressing disgust even when the actually presented face expresses a different emotion. Overall, our findings shed light on the nature of the deficit in facial expression recognition in Huntington's disease mutation-carriers as well as underscore the importance of context in emotion perception.

Seeing with profoundly deactivated mid-level visual areas: non-hierarchical functioning in the human visual cortex.

A fundamental concept in visual processing is that activity in high-order object-category distinctive regions (e.g., lateral occipital complex, fusiform face area, middle temporal+) is dependent on bottom-up flow of activity in earlier retinotopic areas (V2, V3, V4) whose main input originates from primary visual cortex (V1). Thus, activity in down stream areas should reflect lower-level inputs. Here we qualify this notion reporting case LG, a rare case of developmental object agnosia and prosopagnosia. In this person, V1 was robustly activated by visual stimuli, yet intermediate areas (V2-V4) were strongly deactivated. Despite this intermediate deactivation, activity in down stream visual areas remained robust, showing selectivity for houses and places, while selectivity for faces and objects was impaired. The extent of impairment evident in functional magnetic resonance imaging and electroencephalography activations was somewhat larger in the left hemisphere. This pattern of brain activity, coupled with fairly adequate everyday visual performance is compatible with models emphasizing the role of nonlinear local "amplification" of neuronal inputs in eliciting activity in ventral and dorsal visual pathways as well as perceptual experience in the human brain. Thus, while the proper functioning of intermediate areas appears essential for specialization in the cortex, daily visual behavior and reading are maintained even with deactivated intermediate visual areas.

The wide window of face detection.

Faces are detected more rapidly than other objects in visual scenes and search arrays, but the cause for this face advantage has been contested. In the present study, we found that under conditions of spatial uncertainty, faces were easier to detect than control targets (dog faces, clocks and cars) even in the absence of surrounding stimuli, making an explanation based only on low-level differences unlikely. This advantage improved with eccentricity in the visual field, enabling face detection in wider visual windows, and pointing to selective sparing of face detection at greater eccentricities. This face advantage might be due to perceptual factors favoring face detection. In addition, the relative face advantage is greater under flanked than non-flanked conditions, suggesting an additional, possibly attention-related benefit enabling face detection in groups of distracters.