Recruitment of Control and Representational Components of the Semantic System during Successful and Unsuccessful Access to Complex Factual Knowledge.

Our ability to effectively retrieve complex semantic knowledge meaningfully impacts our daily lives, yet the neural processes that underly successful access and transient failures in access remain only partially understood. In this fMRI study, we contrast activation during successful semantic access, unsuccessful semantic access because of transient access failures (i.e., "tip-of-the-tongue," "feeling-of-knowing"), and trials where the semantic knowledge was not possessed. Twenty-four human participants (14 female) were presented 240 trivia-based questions relating to person, place, object, or scholastic knowledge domains. Analyses of the recall event indicated a relatively greater role of a dorsomedial section of the prefrontal cortex in unsuccessful semantic access and relatively greater recruitment of the pars orbitalis of the inferior frontal gyrus in successful access. Successful access was also associated with increased activation in knowledge domain-selective areas. Generally, knowledge domain-selective areas showed increased responses for both preferred and nonpreferred stimulus classes. The exception was place-selective regions (parahippocampal gyrus, transverse occipital sulcus, retrosplenial complex), which were recruited during unsuccessful access attempts for all stimulus domains. Collectively, these results suggest that prefrontal semantic control systems and classical spatial knowledge-selective regions work together to locate relevant information and that access to complex knowledge results in a broad activation of semantic representation extending to regions selective for other knowledge domains.SIGNIFICANCE STATEMENT The ability to access the deep factual knowledge we possess has a meaningful influence on our scholastic, professional, and social lives. In this fMRI study, we investigate the neural processes associated with successful access to this knowledge as well as transient failures in semantic access (tip-of-the-tongue/feeling-of-knowing). Participants attempted to answer trivia-style general knowledge questions drawn from four different knowledge domains. Results suggest that prefrontal semantic control systems and classical spatial knowledge-selective regions work to locate relevant information and that access to complex knowledge results in a broad activation of semantic representation extending to regions selective for other knowledge domains.

fMRI-Indexed neural temporal tuning reveals the hierarchical organsiation of the face and person selective network.

Recognising and knowing about conspecifics is vital to human interaction and is served in the brain by a well-characterised cortical network. Understanding the temporal dynamics of this network is critical to gaining insight into both hierarchical organisation and regional coordination. Here, we combine the high spatial resolution of fMRI with a paradigm that permits investigation of differential temporal tuning across cortical regions. We cognitively under- and overload the system using the rapid presentation (100-1200msec) of famous faces and buildings. We observed an increase in activity as presentation rates slowed and a negative deflection when inter-stimulus intervals (ISIs) were extended to longer periods. The primary distinction in tuning patterns was between core (perceptual) and extended (non-perceptual) systems but there was also evidence for nested hierarchies within systems, as well as indications of widespread parallel processing. Extended regions demonstrated common temporal tuning across regions which may indicate coordinated activity as they cooperate to manifest the diverse cognitive representation accomplished by this network. With the support of an additional psychophysical study, we demonstrated that ISIs necessary for different levels of semantic access are consistent with temporal tuning patterns. Collectively, these results show that regions of the person-knowledge network operate over different temporal timescales consistent with hierarchical organisation.

fMRI response to automatic and purposeful familiar-face processing in perceptual and nonperceptual cortical regions.

Viewing the faces of familiar people selectively activates a distributed network of brain regions implicated in both the perceptual and nonperceptual processing of conspecifics. In this functional magnetic resonance imaging (fMRI) study, we investigate the influence of depth of famous-face processing on this network, comparing a passive incidental face processing to a task that required the extraction of identity and biographic information. We observed that the precuneus, ventromedial prefrontal cortex (vmPFC), anterior temporal face patch (ATFP), and the amygdala exhibit a selective response even during incidental face processing. At the same time, face selectivity was enhanced in the lateral anterior temporal lobe (latATL) and the posterior superior temporal sulcus (pSTS) when identity and information extraction was required. In addition, goal-directed identity and information extraction was associated with a recruitment of inferior frontal gyrus (IFG), whereas this region was deactivated during passive viewing. Collectively, these results show that: 1) in addition to active information extraction, the extended system is recruited by the passive retrieval of person-related knowledge and 2) active access to such knowledge modulates activity in latATL and pSTS, potentially mediated via control circuits in the IFG.NEW & NOTEWORTHY Information is extracted from familiar faces in both automatic and active modes. Using functional MRI, we show: 1) that automatic access results in the selective activation of nonperceptual brain regions, the precuneus, ventromedial prefrontal cortex, and the anterior face patch and amygdala, demonstrating the automaticity of access to information in these regions; 2) selective increases in the activation of the lateral anterior temporal lobe and posterior superior temporal gyrus when biographic information is actively extracted.

Bottom-up and top-down visuomotor responses to action observation.

Action observation produces automatic "mirror" responses in the observers' motor system. However, in daily life, nonimitative actions are often required to be produced in response to others' acts, generating a conflict between automatic and voluntary responses. First, we used single-pulse transcranial magnetic stimulation (TMS) to assess the temporal dynamics of motor output in healthy volunteers preparing rule-based counter-imitative motor responses cued by different observed hand movements. Second, we applied the same paradigm after 1-Hz repetitive TMS (rTMS) of the left posterior parietal cortex (PPC) and of the left dorsolateral prefrontal cortex (dlPFC). The results showed an early (150 ms from onset of visual stimuli) stimulus-driven mirror response that was followed by a later (300 ms) rule-based nonmirror response. rTMS applied to the PPC modulated only the early mirror response. Conversely, rTMS to the dlPFC modulated specifically the late rule-based motor response. The data indicate that a fast bottom-up process mediated by the dorsal visual stream produces automatic imitative responses. Arbitrary rule-based visuomotor associations are on the contrary mediated by a slower system, relying on the prefrontal cortex. The 2 systems are mutually independent and compete for motor output in socially relevant situations only at a distal level.

Person- and place-selective neural substrates for entity-specific semantic access.

Object-category has a pronounced effect on the representation of objects in higher level visual cortex. However, the influence of category on semantic/conceptual processes is less well characterized. In the present study, we conduct 2 fMRI experiments to investigate the semantic processing of information specific to individual people and places (entities). First, during picture presentation, we determined which brain regions show category-selective increases during access to entity-specific semantic information (i.e., nationality) in comparison to general-category discrimination (person vs. place). In the second experiment, we presented either words or pictures to assess the independence of entity-specific category-selective semantic representations from the processes used to access those representations. Convergent results from these 2 experiments show that brain regions exhibiting a category-selective increase during entity-specific semantic access are the same as those that show a supramodal (word/picture) category-selective response during the same task. These responses were different from classical "perceptual" category-selective responses and were evident in the medial precuneus for people and in the retrosplenial complex as well as anterior/superior sections of the transverse occipital sulcus and parahippocampal gyrus for places. These results reveal the pervasive influence of object-category in cortical organization, which extends to aspects of semantic knowledge arbitrarily related to physical/perceptual properties.

Tool-use reshapes the boundaries of body and peripersonal space representations.

Interaction with objects in the environment typically requires integrating information concerning the object location with the position and size of body parts. The former information is coded in a multisensory representation of the space around the body, a representation of peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR). Using a tool to act upon relatively distant objects extends PPS representation. This effect has been interpreted as indicating that tools can be incorporated into BR. However, empirical data showing that tool-use simultaneously affects PPS representation and BR are lacking. To study this issue, we assessed the extent of PPS representation by means of an audio-tactile interaction task and BR by means of a tactile distance perception task and a body-landmarks localisation task, before and after using a 1-m-long tool to reach far objects. Tool-use extended the representation of PPS along the tool axis and concurrently shaped BR; after tool-use, subjects perceived their forearm narrower and longer compared to before tool-use, a shape more similar to the one of the tool. Tool-use was necessary to induce these effects, since a pointing task did not affect PPS and BR. These results show that a brief training with a tool induces plastic changes both to the perceived dimensions of the body part acting upon the tool and to the space around it, suggesting a strong overlap between peripersonal space and body representation.

Whole-brain haemodynamic after-effects of 1-Hz magnetic stimulation of the posterior superior temporal cortex during action observation.

The posterior superior temporal sulcus (pSTS) is active when observing biological motion. We investigated the functional connections of the pSTS node within the action observation network by measuring the after-effect of focal repetitive transcranial magnetic stimulation (rTMS) with whole-brain functional magnetic resonance imaging (fMRI). Participants received 1-Hz rTMS over the pSTS region for 10 min and underwent fMRI immediately after. While scanned, they were shown short video clips of a hand grasping an object (grasp clips) or moving next to it (control clips). rTMS-fMRI was repeated for four consecutive blocks. In two blocks we stimulated the left pSTS region and in the other two the right pSTS region. For each side TMS was applied with an effective intensity (95 % of motor threshold) or with ineffective intensity (50 % of motor threshold). Brain regions showing interactive effects of (clip type) × (TMS intensity) were identified in the lateral temporo-occipital cortex, in the anterior intraparietal region and in the ventral premotor cortex. Remote effects of rTMS were mostly limited to the stimulated hemisphere and consisted in an increase of blood oxygen level-dependent responses to grasp clips compared to control clips. We show that the pSTS occupies a pivotal relay position during observation of goal-directed actions.

Task-based activation and resting-state connectivity predict individual differences in semantic capacity for complex semantic knowledge.

Our ability to know and access complex factual information has far reaching effects, influencing our scholastic, professional and social lives. Here we employ functional MRI to assess the relationship between individual differences in semantic aptitude in the task-based activation and resting-state functional connectivity. Using psychometric and behavioural measures, we quantified the semantic and executive aptitude of individuals and had them perform a general-knowledge semantic-retrieval task (N = 41) and recorded resting-state data (N = 43). During the semantic-retrieval task, participants accessed general-knowledge facts drawn from four different knowledge-domains (people, places, objects and 'scholastic'). Individuals with greater executive capacity more strongly recruit anterior sections of prefrontal cortex (PFC) and the precuneus, and individuals with lower semantic capacity more strongly activate a posterior section of the dorsomedial PFC (dmPFC). The role of these regions in semantic processing was validated by analysis of independent resting-state data, where increased connectivity between a left anterior PFC and the precuneus predict higher semantic aptitude, and increased connectivity between left anterior PFC and posterior dmPFC predict lower semantic aptitude. Results suggest that coordination between core semantic regions in the precuneus and anterior prefrontal regions associated with executive processes support greater semantic aptitude.

Combining concepts across categorical domains: a linking role of the precuneus.

The human capacity for semantic knowledge entails not only the representation of single concepts but the capacity to combine these concepts into the increasingly complex ideas that underlie human thought. This process involves not only the combination of concepts from within the same semantic category but frequently the conceptual combination across semantic domains. In this fMRI study (N=24) we investigate the cortical mechanisms underlying our ability to combine concepts across different semantic domains. Using five different semantic domains (People, Places, Food, Objects and Animals), we present sentences depicting concepts drawn from a single semantic domain as well as sentences that combine concepts from two of these domains. Contrasting single-category and combined-category sentences reveals that the precuneus is more active when concepts from different domains have to be combined. At the same time, we observe that distributed category selectivity representations persist when higher-order meaning involves the combination of categories and that this category-selective response is captured by the combination of the single categories composing the sentence. Collectively, these results suggest that the combination of concepts across different semantic domains is mediated by the precuneus, which functions to link together category-selective representations distributed across the cortex.

Representations of conceptual information during automatic and active semantic access.

When we read a word or see an object, conceptual meaning is automatically accessed. However, previous research investigating non-perceptual sensitivity to semantic class has employed active tasks. In this fMRI study, we tested whether conceptual representations in regions constituting the semantic network are invoked during passive semantic access and whether these representations are modulated by the need to access deeper knowledge. Seventeen healthy subjects performed a semantically active typicality judgment task and a semantically passive phonetic decision task, in both the written and the spoken input-modalities. Stimuli consisted of one hundred forty-four concepts drawn from six semantic categories. Multivariate Pattern Analysis (MVPA) revealed that the left posterior middle temporal gyrus (pMTG), posterior ventral temporal cortex (pVTC) and pars triangularis of the left inferior frontal gyrus (IFG) showed a stronger sensitivity to semantic category when active rather than passive semantic access is required. Using a cross-task training/testing classifier, we determined that conceptual representations were not only active in these regions during passive semantic access but that the neural representation of these categories was common to both active and passive access. Collectively, these results show that while representations in the pMTG, pVTC and IFG are strongly modulated by active conceptual access, consistent representational patterns are present during active and passive conceptual access in these same regions.

Everyday use of the computer mouse extends peripersonal space representation.

Auditory and tactile stimuli are integrated within a limited space around the body to form an auditory peripersonal space (APPS). Here we investigate whether the APPS representation around the hand can be extended through the use of a common technological tool such as the computer mouse. When using a mouse, an action occurring in the space around the hand has a distal effect in the space defined by the computer screen; thus, the mouse virtually links near and far space. Does prolonged experience with the mouse durably extend APPS representation to the far space? We examined 16 habitual mouse users to determine whether a sound presented near the right hand or near the computer screen affected reaction times to a tactile target at the hand. When subjects sat in front of the computer, without holding the mouse, they responded faster to tactile stimuli when sounds were presented near the hand rather than near the screen, consistent with a normal segregation of APPS around the hand. In contrast, when subjects either actively used or even passively held the mouse, the difference between the effects of near and far sounds disappeared, thus showing an extension of the APPS toward the far space. This effect was selective for the effector used to operate the mouse: if tactile stimuli were presented on the left hand, rarely used to act upon the mouse, a sound presented near the hand speeded up reactions times when subjects both held and did not hold the mouse in their left hand.