Lucia Amoruso

Motor-language coupling: direct evidence from early Parkinson’s disease and intracranial cortical recordings

Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinsons disease - EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments suggest the presence of a motor-language network which is not restricted to somatotopically defined brain areas. These results open new pathways in the fields of motor diseases, theoretical approaches to language understanding, and models of action-perception coupling.

Action-verb processing in Parkinson’s disease: new pathways for motor–language coupling

Recent studies suggest that action-verb processing is particularly affected in early stage Parkinson’s disease (PD), highlighting the potential role of subcortical areas in language processing and in the semantic integration of actions. However, this disorder-related language impairment is frequently unrecognized by clinicians and often remains untreated. Early detection of action-language processing deficits could be critical for diagnosing and developing treatment strategies for PD. In this article, we review how action-verb processing is affected in PD and propose a model in which multiple and parallel frontotemporal circuits between the cortex and the basal ganglia provide the anatomic substrate for supporting action-language processing. We hypothesize that contextual coupling of action-language networks are partially dependent on cortical–subcortical integration, and not only on somatotopic motor cortical organization or in a mirror neuron system. This hypothesis is supported by both experimental and clinical evidence. Then, we identify further research steps that would help to determine the reliability of action-language impairments as an early marker of PD. Finally, theoretical implications for clinical assessment and for models of action-language interaction (action–perception cycle theories, mirror system models of language, and embodied cognition approaches to language) are discussed.

How embodied is action language? Neurological evidence from motor diseases

Although motor-language coupling is now being extensively studied, its underlying mechanisms are not fully understood. In this sense, a crucial opposition has emerged between the non-representational and the representational views of embodiment. The former posits that action language is grounded on the non-brain motor system directly engaged by musculoskeletal activity - i.e., peripheral involvement of ongoing actions. Conversely, the latter proposes that such grounding is afforded by the brains motor system - i.e., activation of neural areas representing motor action. We addressed this controversy through the action-sentence compatibility effect (ACE) paradigm, which induces a contextual coupling of motor actions and verbal processing. ACEs were measured in three patient groups - early Parkinsons disease (EPD), neuromyelitis optica (NMO), and acute transverse myelitis (ATM) patients - as well as their respective healthy controls. NMO and ATM constitute models of injury to non-brain motor areas and the peripheral motor system, whereas EPD provides a model of brain motor system impairment. In our study, EPD patients exhibited impaired ACE and verbal processing relative to healthy participants, NMO, and ATM patients. These results indicate that the processing of action-related words is mainly subserved by a cortico-subcortical motor network system, thus supporting a brain-based embodied view on action language. More generally, our findings are consistent with contemporary perspectives for which action/verb processing depends on distributed brain networks supporting context-sensitive motor-language coupling.

N400 ERPs for actions: building meaning in context

Converging neuroscientific evidence suggests the existence of close links between language and sensorimotor cognition. Accordingly, during the comprehension of meaningful actions, our brain would recruit semantic-related operations similar to those associated with the processing of language information. Consistent with this view, electrophysiological findings show that the N400 component, traditionally linked to the semantic processing of linguistic material, can also be elicited by action-related material. This review outlines recent data from N400 studies that examine the understanding of action events. We focus on three specific domains, including everyday action comprehension, co-speech gesture integration, and the semantics involved in motor planning and execution. Based on the reviewed findings, we suggest that both negativities (the N400 and the action-N400) reflect a common neurocognitive mechanism involved in the construction of meaning through the expectancies created by previous experiences and current contextual information. To shed light on how this process is instantiated in the brain, a testable contextual fronto-temporo-parietal model is proposed.

The face and its emotion: Right N170 deficits in structural processing and early emotional discrimination in schizophrenic patients and relatives

Previous studies have reported facial emotion recognition impairments in schizophrenic patients, as well as abnormalities in the N170 component of the event-related potential. Current research on schizophrenia highlights the importance of complexly-inherited brain-based deficits. In order to examine the N170 markers of face structural and emotional processing, DSM-IV diagnosed schizophrenia probands (n=13), unaffected first-degree relatives from multiplex families (n=13), and control subjects (n=13) matched by age, gender and educational level, performed a categorization task which involved words and faces with positive and negative valence. The N170 component, while present in relatives and control subjects, was reduced in patients, not only for faces, but also for face-word differences, suggesting a deficit in structural processing of stimuli. Control subjects showed N170 modulation according to the valence of facial stimuli. However, this discrimination effect was found to be reduced both in patients and relatives. This is the first report showing N170 valence deficits in relatives. Our results suggest a generalized deficit affecting the structural encoding of faces in patients, as well as the emotion discrimination both in patients and relatives. Finally, these findings lend support to the notion that cortical markers of facial discrimination can be validly considered as vulnerability markers.

Beyond Extrastriate Body Area (EBA) and Fusiform Body Area (FBA): Context Integration in the Meaning of Actions

Our ability to identify and interpret the actions and intentions of other people in a meaningful way is the bedrock of social cognition. Visual perception of human body is a critical component of this complex task as long as it provides cues which enable the observer to make the required inferences to accurately extract the meaning of daily action events. During the last decade, neuroimaging studies have identified two brain regions of the extrastriate visual cortex that are highly sensitive to the perception of human bodies and body parts. These regions are the extrastriate body area (EBA), located at the posterior inferior temporal sulcus/middle temporal gyrus (Downing et al., 2001) and the fusiform body area (FBA) found ventrally in the fusiform gyrus (Peelen and Downing, 2005; Schwarzlose et al., 2005). Evidence derived from fMRI studies has shown that both areas become significantly activated in response to body/body parts stimuli visually presented in different formats like photos, line drawings, stick figures, and silhouettes compared to control stimuli like faces/face parts, tools/tool parts, and scenes (Downing et al., 2001; Peelen and Downing, 2005; Schwarzlose et al., 2005; Spiridon et al., 2006; Weiner and Grill-Spector, 2010). Recently, it has been suggested that EBA and FBA can be functionally dissociated, with a more selective activation for local body parts in EBA relative to more holistic images of the human body in FBA (Taylor et al., 2007). Based on these findings, many authors have claimed that EBA/FBA should be directly involved in complex functions such as perceiving goal-directed actions and other higher-level related processes (Costantini et al., 2005; Saxe et al., 2006; Moro et al., 2008; Marsh et al., 2010; Kuhn et al., 2011). However, as suggested by Downing and Peelen (2011), it might be more accurate to interpret the activity of these regions in terms of populations of neurons that selectively encode and make explicit low-level visual features of human bodies like body shape and posture. According to this hypothesis, the comprehension of meaningful actions could be supported by a more distributed neural network where visual information extracted by EBA/FBA is integrated with the contextual information processed in other parts of the brain. Although this hypothesis seems to be more plausible, the authors do not give further information on how this integration might be accomplished or, more specifically, about which other cortical areas would be actively engaged in this network. In order to address this issue, we propose a functional neuroanatomic model for the contextual processing of goal-directed actions where the general perceptual processing provided by EBA/FBA is integrated in a larger fronto-insular–temporal network. When we witness a simple event, our brain integrates the information about people, objects, and the interactions among them into a coherent meaningful representation. For instance, object recognition is thought to be instantiated by cognitive structures that integrate information about the identity of the objects that tend to co-occur in a given context with previously learned information about their possible relationships (Bar, 2004). These structures can be thought of as a set of expectations about what is more probable to see or not to see in a given context, enabling us to make predictions and accurately disambiguate incoming information. We proposed that in a fronto-insular–temporal “social context network” (SCN), several frontal areas update and associate ongoing contextual information in relation to episodic memory and target-context associations (Sigala et al., 2008; Bar, 2009; Burgess et al., 2009). The temporal regions [e.g., the parahippocampal cortex (PHC), hippocampus, and amygdala] may index the value learning of target-context associations (Langston and Wood, 2010). Finally, the insular cortex would coordinate internal and external milieus in an inner motivational state (Singer et al., 2009; Ibanez et al., 2010a). See Figure ​Figure11. Figure 1 Lateral view of the left hemisphere showing the proposed fronto-insular–temporal network (light-blue, violet, and green regions of interest, respectively). In this context network, prefrontal areas (PFC) such as frontopolar and dorsolateral prefrontal ... This contextual dimension of action understanding is also supported by ERP studies on the N400-like component, an ongoing negativity elicited when a meaningful action is incongruent (unexpected) with a previous context. N400 seems to be a specific context integration component (Bar, 2004). For example, videos and pictures of everyday-life actions, co-speech gestures, and semantic processing of current motor events (Sitnikova et al., 2003; Aravena et al., 2010; Ibanez et al., 2010b, 2011; Proverbio et al., 2010) have shown that, as the action-related stimulus becomes more expected/congruent with the context in which it is embedded, the N400 amplitude is reduced compared to incongruent/unexpected conditions. These findings suggest that when the previous context builds up meaning, processing of upcoming stimulus that fit with that context is facilitated. Evidence derived from lesion studies, MEG, and intracranial recordings includes the left superior/middle temporal gyrus, the anterior-medial temporal lobe, the PHC and fusiform gyrus as well as frontopolar, orbital, and dorsolateral prefrontal regions as the possible sources of this N400 effect (Halgren et al., 2002; Van Petten and Luka, 2006). Finally, as well as frontal and temporal regions, the insular cortex plays a crucial role in the proposed network. This region has been recently implicated in the contextual integration of interoceptive information (conscious representation about ones body physiological state and motivational drives) with external stimuli (sensory current environment) into a global feeling state (Craig, 2002; Ibanez et al., 2010a). Moreover, anterior insular cortex has also shown to be recruited during motivational decision-making in uncertain contexts, suggesting that this area also mediates risk behavior when the available information is not sufficient to predict an outcome (Singer et al., 2009). Overall, the SCN provides an empirically testable set of hypotheses regarding contextual update, contextual prediction, and target-context association in action meaning paradigms. For instance, we expect to observe the engagement of the SCN during action meaning processing. This prediction is partially confirmed since frontal, temporal, or insular activations have been previously observed together with EBA and FBA during action paradigms (Kable and Chatterjee, 2006; Lamm et al., 2007; Lamm and Decety, 2008; Hodzic et al., 2009a,b; Cross et al., 2010; Kret et al., 2011). Additionally, a more straight empirical testing would be provided by direct contextual manipulation of action-related stimuli. The use of frames, background information or multimodal designs (as used in other domains of contextual studies, e.g., Bar, 2004) adapted to action meaning tasks would provide simple experimental shortcuts. An ideal experimental approach would comprise a battery of tasks that vary the degree of context for action/non-action stimuli, in order to test the relative engagement of the SCN in EBA/FBA activation during action and non-action processing. We expect that, while manipulating the contextual information (e.g., by increasing its influence), stronger activation in frontal, temporal, and insular regions rather than in EBA/FBA would be observed. Furthermore, if the contextual information being processed crucially requires the extraction of specific information regarding body/body parts (e.g., imagine a task where body posture is important for disentangle the emotional state of a person), we expect that activity in EBA/FBA will be enhanced as much as in the other regions of the SCN. In brief, we suggest that action meaning is beyond EBA and FBA through the integration of contextual information processed by a distributed fronto-insular–temporal network. Moreover, action meaning is not an amodal, invariant, immutable representation in a brain area, but instead a polymodal, context-sensitive, constructive, and distributed process. Similar to context integration during visual object recognition (Bar, 2004), information of body appearance and posture in EBA/FBA should be integrated within a SCN in order to process action meaning. We propose a multimodal system of action meaning in which expectations (frontal areas) of external information (including body processing in EBA/FBA), interacts with their semantic association (temporal regions) and the current internal motivational states (insula) in order to get a specific significance of an event. Thus, a context–facilitation large-scale distributed neural network may process and influence the EBA/FBA activity in a top-down manner.

Time to Tango: Expertise and contextual anticipation during action observation

Predictive theories of action observation propose that we use our own motor system as a guide for anticipating and understanding other peoples actions through the generation of context-based expectations. According to this view, people should be better in predicting and interpreting those actions that are present in their own motor repertoire compared to those that are not. We recorded high-density event-related potentials (ERPs: P300, N400 and Slow Wave, SW) and source estimation in 80 subjects separated by their level of expertise (experts, beginners and naïves) as they observed realistic videos of Tango steps with different degrees of execution correctness. We also performed path analysis to infer causal relationships between ongoing anticipatory brain activity, evoked semantic responses, expertise measures and behavioral performance. We found that anticipatory activity, with sources in a fronto-parieto-occipital network, early discriminated between groups according to their level of expertise. Furthermore, this early activity significantly predicted subsequent semantic integration indexed by semantic responses (N400 and SW, sourced in temporal and motor regions) which also predicted motor expertise. In addition, motor expertise was a good predictor of behavioral performance. Our results show that neural and temporal dynamics underlying contextual action anticipation and comprehension can be interpreted in terms of successive levels of contextual prediction that are significantly modulated by subjects prior experience.

Organization of brain networks governed by long-range connections index autistic traits in the general population

BackgroundThe dimensional approach to autism spectrum disorder (ASD) considers ASD as the extreme of a dimension traversing through the entire population. We explored the potential utility of electroencephalography (EEG) functional connectivity as a biomarker. We hypothesized that individual differences in autistic traits of typical subjects would involve a long-range connectivity diminution within the delta band.MethodsResting-state EEG functional connectivity was measured for 74 neurotypical subjects. All participants also provided a questionnaire (Social Responsiveness Scale, SRS) that was completed by an informant who knows the participant in social settings. We conducted multivariate regression between the SRS score and functional connectivity in all EEG frequency bands. We explored modulations of network graph metrics characterizing the optimality of a network using the SRS score.ResultsOur results show a decay in functional connectivity mainly within the delta and theta bands (the lower part of the EEG spectrum) associated with an increasing number of autistic traits. When inspecting the impact of autistic traits on the global organization of the functional network, we found that the optimal properties of the network are inversely related to the number of autistic traits, suggesting that the autistic dimension, throughout the entire population, modulates the efficiency of functional brain networks.ConclusionsEEG functional connectivity at low frequencies and its associated network properties may be associated with some autistic traits in the general population.

Contextual Impairments in Schizophrenia and the FN400

Our brains are good at extracting and processing social contextual cues. Ongoing information is rapidly linked to memory traces of previous experiences, allowing us to generate predictions which help us interpret daily situations. These predictions are a core aspect of human cognition as long as they make social behaviors more efficient. Current evidence, however, suggests that schizophrenia patients are less able to benefit from context and, consequently, social impairments are commonly observed in this complex disorder. Over the last decades, event-related potentials (ERPs) have been used to investigate the electrophysiological correlates of several memory processes. In classical explicit memory experiments, familiarity (the subjective experience of knowing an item – e.g., a face-without being able to retrieve any further episodic information) has been associated with a mid-frontal old/new difference occurring in the 300–500 ms window, often called “FN400” (Rugg and Curran, 2007). For example, the comparison of ERPs on hits and correct rejections (old/new effects) during face recognition, lead to higher FN400 amplitudes for correctly rejected new items than for correctly recognized old ones. Importantly, this difference is observed despite recognition is followed by the recollection of specific details associated to the item (e.g., occupations associated with the faces, Curran and Hancock, 2007). This lack of ability in retrieving episodic details is attributed to the fact that it is perceived out of the context in which is commonly embedded. Recently, Guillaume et al. (2012) have investigated FN400 old/new effects in schizophrenia during face recognition. The aim of their study was to evaluate if familiarity was affected by contextual information mismatching in schizophrenia patients versus controls by manipulating the background in which faces appeared. This resulted in three conditions: old (faces that were presented on the study phase with the same background), different (faces that were presented on the study phase with a different background), and new condition (faces that were not presented on the study phase). They found that, across conditions, schizophrenia patients showed greater FN400 amplitude compared to controls. Moreover, in the patients, the FN400 amplitude was the same in the different and new conditions suggesting that familiarity was severely disrupted when the context in which faces appeared was changed. Although correlates of familiarity have been classically linked to the FN400 (Rugg and Curran, 2007), recent work (Voss et al., 2012) has called into question this traditionally accepted linkage, suggesting that modulations in this component could be actually indexing implicit conceptual memory processing instead of familiarity per se. It is important to note that the “F” in FN400 indicates a more frontal topographical distribution compared to the similar N400 component found for words semantically anomalous to the preceding context. While this difference in the scalp activity is consistent with the existence of distinct roles for each negativity (FN400 in familiarity versus N400 in language), it has been suggested (Kutas and Federmeier, 2011) that the classical N400 and the FN400 could be indexing an analog process. In our view, both proposals are justified and can explain, in a more parsimonious fashion, current FN400-related data. However, based on the possible functional analogy between the FN400 and the N400 and also on current neuroanatomical evidence suggesting frontal and temporal sources (Halgren et al., 2002; Voss et al., 2008; Ibanez et al., 2012), we propose that this component might be reflecting a more general process regarding implicit contextual facilitation. We have recently proposed that the N400 reflects the activation of a contextual frontotemporal network responsible for the instantiation of meaning construction under the crucial role of context-based information (Amoruso et al., 2011; Ibanez and Manes, 2012). In our model, similar to the one proposed by Bar (2004) for object recognition, frontal regions would play a key role in updating ongoing contextual information in working memory and integrating it with semantic knowledge about target-context associations and their learning value stored in temporal regions. Taken together, information about current and previous experiences is used by the brain in order to make focused predictions to facilitate the interpretation of the ongoing situation. Furthermore, our model is supported by current experimental evidence from electrocorticography (ECoG) direct recordings (Ibanez et al., 2012) and source estimation (Halgren et al., 2002) which suggests that the scalp-recorded N400 reflects the coordinated activity of multiple brain areas, including temporal and frontal regions. Importantly, these two regions, also thought to be involved in the FN400 generation (Voss et al., 2012), are the most affected in schizophrenia, at structural, and functional level (Wong and Van Tol, 2003). Contextual deficits seem to be the core of N400 abnormal modulations found in schizophrenia (Kumar and Debruille, 2004; Ibanez et al., 2011). Moreover, contextual impairments seem to be present in this condition, from the basic perceptual level (Chambon et al., 2008) to the higher aspects of social cognition (Chung et al., 2011). FN400 abnormal modulations in schizophrenia patients found by Guillaume et al. (2012) can be explained as a disruption in the integration of contextual cues in the frontotemporal network. More specifically, the greater FN400 amplitude showed by these patients compared to controls suggests that they are not able to benefit from context, maybe due to a reduction in functional connections between frontal and temporal lobes. This aforementioned disruption can be more specifically understood in terms of an inability to maintain a representation of context in working memory (Cohen and Servan-Schreiber, 1999). In this view, the FN400 component would indexes a more general and constructive process regarding implicit context-based facilitation in the brain, a process that is severely disrupted in schizophrenia. By this means, our approach would be able to explain not only normal old-new FN400 effects and N400 classic modulations, but also schizophrenia abnormal ones, providing a broader and unified framework to interpret the N400 findings and the contextual impairments observed in this complex disorder.

Contextual modulation of motor resonance during the observation of everyday actions.

Neuroimaging studies on action observation suggest that context plays a key role in coding high-level components of motor behavior, including the short-term and the end-goal of an action. However, little is known about the possible role of context in shaping lower-levels of action processing such as reading action kinematics and simulating muscular activity. Here, we combined single-pulse TMS and motor-evoked potentials (MEPs) recording to explore whether top-down contextual information is capable of modulating low-level motor representations. We recorded MEPs from FDI and FCR muscles while participants watched videos about everyday actions embedded in congruent, incongruent or ambiguous contexts. Videos were interrupted before action ending, and participants were requested to predict the course of the observed action. A contextual modulation of corticospinal excitability was observed only for the FDI muscle, which is specifically involved in the execution of reaching-to-grasping movements, and whose corticospinal pathway is influenced by the observation of the very same movements. This modulation was reflected in a selective decrease of corticospinal excitability during the observation of actions embedded in incongruent as compared to congruent and ambiguous contexts. These findings indicate that motor resonance is not an entirely automatic process, but it can be modulated by high-level contextual representations.