Neural underpinnings of processing combinatorial unstated meaning and the influence of individual cognitive style.

We investigated the neurocognitive mechanisms underlying the processing of combinatorial unstated meaning. Sentences like "Charles jumped for 5 minutes." engender an iterative meaning that is not explicitly stated but enriched by comprehenders beyond simple composition. Comprehending unstated meaning involves meaning contextualization-integrative meaning search in sentential-discourse context. Meanwhile, people differ in how they process information with varying context sensitivity. We hypothesized that unstated meaning processing would vary with individual socio-cognitive propensity indexed by the Autism-Spectrum Quotient (AQ), accompanied by differential cortical engagements. Using functional magnetic resonance imaging, we examined the processing of sentences with unstated iterative meaning in typically-developed individuals and found an engagement of the fronto-parietal network, including the left pars triangularis (L.PT), right intraparietal (R.IPS), and parieto-occipital sulcus (R.POS). We suggest that the L.PT subserves a contextual meaning search, while the R.IPS/POS supports enriching unstated iteration in consideration of event durations and interval lengths. Moreover, the activation level of these regions negatively correlated with AQ. Higher AQ ties to lower L.PT activation, likely reflecting weaker context sensitivity, along with lower IPS activation, likely reflecting weaker computation of events' numerical-temporal specifications. These suggest that the L.PT and R.IPS/POS support the processing of combinatorial unstated meaning, with the activation level modulated by individual cognitive styles.

When a sentence loses semantics: Selective involvement of a left anterior temporal subregion in semantic processing.

Although the left anterior temporal lobe (ATL) has been associated with semantic processing, the role of this region in syntactic structure building of sentences remains a subject of debate. Functional neuroimaging studies contrasting well-formed sentences with word lists lacking syntactic structure have produced mixed results. The current functional magnetic resonance imaging study examined whether the left ATL is selectively involved in semantic processing or also plays a role in syntactic structure building by manipulating syntactic complexity and meaningfulness in a novel way. To deprive semantic/pragmatic information from a sentence, we replaced all content words with pronounceable meaningless placeholders. We conducted an experiment with a 2 × 2 factorial design with factors of SEMANTICS (natural sentences [NAT]; sentences with placeholders [SPH]) and SYNTAX (the basic Japanese Subject-Object-Verb [SOV] word order; a changed Object-Subject-Verb [OSV] word order). A main effect of SEMANTICS (NAT > SPH) was found in the left ATL, as well as in the ventral occipitotemporal regions. The opposite contrast (SPH > NAT) revealed activation in the dorsal regions encompassing Brodmann area 44, the premotor area, and the parietal cortex in the left hemisphere. We found no main effect of SYNTAX (OSV > SOV) in a subregion of the left ATL that was more responsive to natural sentences than meaningless sentences. These results indicate selective involvement of a subregion of the left ATL in semantic/pragmatic processing.

The Motor Network Reduces Multisensory Illusory Perception.

Observing mouth movements has strikingly effects on the perception of speech. Any mismatch between sound and mouth movements will result in listeners perceiving illusory consonants (McGurk effect), whereas matching mouth movements assist with the correct recognition of speech sounds. Recent neuroimaging studies have yielded evidence that the motor areas are involved in speech processing, yet their contributions to multisensory illusion remain unclear. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in an event-related design, we aimed to identify the functional roles of the motor network in the occurrence of multisensory illusion in female and male brains. fMRI showed bilateral activation of the inferior frontal gyrus (IFG) in audiovisually incongruent trials. Activity in the left IFG was negatively correlated with occurrence of the McGurk effect. The effective connectivity between the left IFG and the bilateral precentral gyri was stronger in incongruent than in congruent trials. The McGurk effect was reduced in incongruent trials by applying single-pulse TMS to motor cortex (M1) lip areas, indicating that TMS facilitates the left IFG-precentral motor network to reduce the McGurk effect. TMS of the M1 lip areas was effective in reducing the McGurk effect within the specific temporal range from 100 ms before to 200 ms after the auditory onset, and TMS of the M1 foot area did not influence the McGurk effect, suggesting topographical specificity. These results provide direct evidence that the motor network makes specific temporal and topographical contributions to the processing of multisensory integration of speech to avoid illusion.SIGNIFICANCE STATEMENT The human motor network, including the inferior frontal gyrus and primary motor cortex lip area, appears to be involved in speech perception, but the functional contribution to the McGurk effect is unknown. Functional magnetic resonance imaging revealed that activity in these areas of the motor network increased when the audiovisual stimuli were incongruent, and that the increased activity was negatively correlated with perception of the McGurk effect. Furthermore, applying transcranial magnetic stimulation to the motor areas reduced the McGurk effect. These two observations provide evidence that the motor network contributes to the avoidance of multisensory illusory perception.

Neural capacity limits during unconscious semantic processing.

A growing body of neuroimaging data suggests that direct measurements of brain activity can reveal subliminal effects that remain invisible with behavior measures alone. We examined whether sentence comprehension processes could be triggered by a sequence of masked words. On each trial, participants viewed a rapid sequence of masked or unmasked words, including a subject noun, three adverbs and followed by a visible target verb. To probe the capacity limits of unconscious processing, we measured event-related potentials associated with the semantic congruency between the noun and the verb, while varying the subject position in each sentence. Unmasked sentences produced significant behavioral effects of congruency, paralleled by robust N400 effects, independently of subject-verb distance. By contrast, masked sentences produced no behavioral effect and elicited N400 effects only when subjects and verbs were separated by 0 or 1 word. The present results suggest that semantic integration of multiple words can occur unconsciously only if the distance between the words to be integrated does not exceed two words. Although the possibility remains that even longer sequence of invisible words may produce similar neural effects in different experimental settings, our ERP data show that only conscious perception gives access to a buffer that enables robust sentence-level processing independently of temporal distance.

Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy.

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Building by Syntax: The Neural Basis of Minimal Linguistic Structures.

Language comes in utterances in which words are bound together according to a simple rule-based syntactic computation (merge), which creates linguistic hierarchies of potentially infinite length-phrases and sentences. In the current functional magnetic resonance imaging study, we compared prepositional phrases and sentences-both involving merge-to word lists-not involving merge-to explore how this process is implemented in the brain. We found that merge activates the pars opercularis of the left inferior frontal gyrus (IFG; Brodmann Area [BA] 44) and a smaller region in the posterior superior temporal sulcus (pSTS). Within the IFG, sentences engaged a more anterior portion of the area (pars triangularis, BA 45)-compared with phrases-which showed activity peak in BA 44. As prepositional phrases, in contrast to sentences, do not contain verbs, activity in BA 44 may reflect structure-building syntactic processing, while the involvement of BA 45 may reflect the encoding of propositional meaning initiated by the verb. The pSTS appears to work together with the IFG during thematic role assignment not only at the sentential level, but also at the phrasal level. The present results suggest that merge, the process of binding words together into syntactic hierarchies, is primarily supported by BA 44 in the IFG.

Processing noncanonical sentences in broca's region: reflections of movement distance and type.

Various noncanonical sentence constructions are derived from basic sentence structures by a phrase displacement called Movement. The moved phrase (filler) leaves a silent copy at the extracted position (gap) and is reactivated when the hearer/reader passes over the gap. Consequently, memory operations are assumed to occur to establish the filler-gap link. For languages that have a relatively free word order like German, a distinct linguistic operation called Scrambling is proposed. Although Movement and Scrambling are assumed to be different linguistic operations, they both involve memory prone filler-gap processes. To clarify whether filler-gap memory processes in Scrambling and Movement differ neuroanatomically, we designed a functional magnetic resonance imaging study and compared the effect of memory load parameterized by filler-gap distance in the 2 sentence types. Here, we show that processing of the 2 sentence types commonly relies on a left hemispheric network consisting of the inferior frontal gyrus, middle part of the middle temporal gyrus, and intraparietal sulcus. However, we found differences for the 2 sentence types in the linearity of filler-gap distance effect. Thus, the present results suggest that the same neural substrate supports the memory processes of sentences constructed by Movement and Scrambling, although differentially modulated by memory load.

Hand shape selection in pantomimed grasping: interaction between the dorsal and the ventral visual streams and convergence on the ventral premotor area.

In visually guided grasping, possible hand shapes are computed from the geometrical features of the object, while prior knowledge about the object and the goal of the action influence both the computation and the selection of the hand shape. We investigated the system dynamics of the human brain for the pantomiming of grasping with two aspects accentuated. One is object recognition, with the use of objects for daily use. The subjects mimed grasping movements appropriate for an object presented in a photograph either by precision or power grip. The other is the selection of grip hand shape. We manipulated the selection demands for the grip hand shape by having the subjects use the same or different grip type in the second presentation of the identical object. Effective connectivity analysis revealed that the increased selection demands enhance the interaction between the anterior intraparietal sulcus (AIP) and posterior inferior temporal gyrus (pITG), and drive the converging causal influences from the AIP, pITG, and dorsolateral prefrontal cortex to the ventral premotor area (PMv). These results suggest that the dorsal and ventral visual areas interact in the pantomiming of grasping, while the PMv integrates the neural information of different regions to select the hand posture. The present study proposes system dynamics in visually guided movement toward meaningful objects, but further research is needed to examine if the same dynamics is found also in real grasping.

Segregating the core computational faculty of human language from working memory.

In contrast to simple structures in animal vocal behavior, hierarchical structures such as center-embedded sentences manifest the core computational faculty of human language. Previous artificial grammar learning studies found that the left pars opercularis (LPO) subserves the processing of hierarchical structures. However, it is not clear whether this area is activated by the structural complexity per se or by the increased memory load entailed in processing hierarchical structures. To dissociate the effect of structural complexity from the effect of memory cost, we conducted a functional magnetic resonance imaging study of German sentence processing with a 2-way factorial design tapping structural complexity (with/without hierarchical structure, i.e., center-embedding of clauses) and working memory load (long/short distance between syntactically dependent elements; i.e., subject nouns and their respective verbs). Functional imaging data revealed that the processes for structure and memory operate separately but co-operatively in the left inferior frontal gyrus; activities in the LPO increased as a function of structural complexity, whereas activities in the left inferior frontal sulcus (LIFS) were modulated by the distance over which the syntactic information had to be transferred. Diffusion tensor imaging showed that these 2 regions were interconnected through white matter fibers. Moreover, functional coupling between the 2 regions was found to increase during the processing of complex, hierarchically structured sentences. These results suggest a neuroanatomical segregation of syntax-related aspects represented in the LPO from memory-related aspects reflected in the LIFS, which are, however, highly interconnected functionally and anatomically.

Pupil Dilation Reflects Emotional Arousal Via Poetic Language.

We investigated pupillary responses to the world's shortest fixed verses, Japanese haiku as aesthetic poetry (AP) and senryu as comic poetry (CP), in comparison with non-poetry control stimuli (NP) comprised of slogans that had the same rhythm patterns. Native Japanese speakers without literary training listened to these stimuli while we recorded their pupil diameters. We found that participants' pupils were significantly dilated for CP compared to NP in an early time window. While AP also evoked larger dilations than NP, the latency for AP-related pupil dilation was relatively long. Thus, lay people experience quick and intense arousal in response to funny and humorous words, while aesthetic properties of words may also elicit intense but slower changes in listeners' arousal levels, presumably because they evoke more implicit and subtle emotional effects. This study is the first to provide evidence that poetic language elicits human pupillary dilation. A better understanding of the cognitive and neural substrates for the sensitive awareness of pleasures expressed via poetic language will provide insights for improving mental and physical health. Hence, pupillometry can act as a useful convenient measurement to delineate the sympathetic activation of emotional contexts via language.

Who was the agent? The neural correlates of reanalysis processes during sentence comprehension.

Sentence comprehension is a complex process. Besides identifying the meaning of each word and processing the syntactic structure of a sentence, it requires the computation of thematic information, that is, information about who did what to whom. The present fMRI study investigated the neural basis for thematic reanalysis (reanalysis of the thematic roles initially assigned to noun phrases in a sentence) and its interplay with syntactic reanalysis (reanalysis of the underlying syntactic structure originally constructed for a sentence). Thematic reanalysis recruited a network consisting of Broca's area, that is, the left pars triangularis (LPT), and the left posterior superior temporal gyrus, whereas only LPT showed greater sensitivity to syntactic reanalysis. These data provide direct evidence for a functional neuroanatomical basis for two linguistically motivated reanalysis processes during sentence comprehension.

Neural control of cross-language asymmetry in the bilingual brain.

Most bilinguals understand their second language more slowly than their first. This behavioral asymmetry may arise from the perceptual, phonological, lexicosemantic, or strategic components of bilingual word processing. However, little is known about the neural source of such language dominance and how it is regulated in the bilingual brain. Using functional magnetic resonance imaging, we found that unconscious neural priming in bilingual word recognition is language nonselective in the left midfusiform gyrus but exhibits a preference for the dominant language in the left posterior middle temporal gyrus (MTG). These early-stage components of reading were located slightly upstream of the left midlateral MTG, which exhibited enhanced response during a conscious switch of language. Effective connectivity analysis revealed that this language switch is triggered by reentrant signals from inferior frontal cortex and not by bottom-up signals from occipitotemporal cortex. We further confirmed that magnetic stimulation of the same inferior frontal region interferes with conscious language control but does not disrupt unconscious priming by masked words. Collectively, our results demonstrate that the neural bottleneck in the bilingual brain is a cross-language asymmetry of form-meaning association in inferolateral temporal cortex, which is overcome by a top-down cognitive control for implementing a task schema in each language.

Graphomotor memory in Exner's area enhances word learning in the blind.

Handwriting is thought to impede vocabulary learning in sighted adults because the motor execution of writing interferes with efficient audiovisual processing during encoding. However, the motor memory of writing may facilitate adult word learning when visual sensory inputs are severely restricted. Using functional MRI, we show that late-blind participants, but not sighted participants, learned novel words by recruiting the left dorsal premotor cortex known as Exner's writing area and its functional coupling with the left hippocampus. During later recall, the phonological and semantic contents of these words are represented in the activation patterns of the left hippocampus as well as in those of left frontotemporal language areas. These findings suggest that motor codes of handwriting help blind participants maintain word-form representations during learning and retrieval. We propose that such reliance on the motor system reflects a broad architecture of the cerebral language network which encompasses the limb motor system as a hardwired component.

Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons.

Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT2A receptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT2A receptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.

Neural architecture of human language: Hierarchical structure building is independent from working memory.

Using functional magnetic resonance imaging (fMRI), we show that the neural substrate of language does not overlap with that for verbal working memory when we carefully define verbal working memory in sentence processing. Object-Subject-Verb (OSV) sentences in Japanese were contrasted with canonical Subject-Object-Verb (SOV) sentences, which had less hierarchy in linguistic structure. This contrast revealed the posterior part of Broca's area and the left posterior middle temporal gyrus (pMTG) as the neural bases for hierarchical structure building. Furthermore, we changed verbal working memory load in OSV sentences by adding modifiers to the subject or object noun phrases; this resulted in the activation in the op9, which is situated in the frontal operculum and is adjacent to, but not situated in, Broca's area. The neuroanatomical segregation of language processing from verbal working memory suggests independence of the faculty of language from the verbal working memory system, providing evidence for the domain-specificity of language in human cognition.

An fMRI study dissociating distance measures computed by Broca's area in movement processing: clause boundary vs. identity.

Behavioral studies of sentence comprehension suggest that processing long-distance dependencies is subject to interference effects when Noun Phrases (NP) similar to the dependency head intervene in the dependency. Neuroimaging studies converge in localizing such effects to Broca's area, showing that activity in Broca's area increases with the number of NP interveners crossed by a moved NP of the same type. To test if NP interference effects are modulated by adding an intervening clause boundary, which should by hypothesis increase the number of successive-cyclic movements, we conducted an fMRI study contrasting NP interveners with clausal (CP) interveners. Our design thus had two components: (I) the number of NP interveners crossed by movement was parametrically modulated; (II) CP-intervention was contrasted with NP-intervention. The number of NP interveners parametrically modulated a cluster straddling left BA44/45 of Broca's area, replicating earlier studies. Adding an intervening clause boundary did not significantly modulate the size of the NP interference effect in Broca's area. Yet, such an interaction effect was observed in the Superior Frontal Gyrus (SFG). Therefore, the involvement of Broca's area in processing syntactic movement is best captured by memory mechanisms affected by a grammatically instantiated type-identity (i.e., NP) intervention.

Both parietal lobes are involved in drawing: a functional MRI study and implications for constructional apraxia.

In clinical studies, many researchers have reported that drawing can be disturbed by left or right unilateral parietal lobe damage (constructional apraxia). There seem to be two possible predictions about the cerebral laterality for drawing. The first is that drawing requires both parietal lobes, therefore, a lesion to either side can disrupt drawing. The second is that individuals can differ in laterality: some have only right or left activations, and some have bilateral. To test these predictions, we investigated with functional magnetic resonance imaging (fMRI) the cerebral activation whilst 17 right-handed healthy subjects performed a drawing task. The experiment consisted of two conditions: (1). naming an object in a presented picture and drawing it by using right index finger (DRAWING & NAMING); (2). naming an object in a presented picture (NAMING). We considered the brain regions that had greater activity in the DRAWING&NAMING condition than in the NAMING condition were the neural substrates of drawing. Individual analysis revealed that all subjects showed parietal activation bilaterally. We interpret that the results support the first prediction that both parietal lobes are required for drawing. By calculating the laterality indices of the individual parietal activations, it was found that there were more left dominant subjects than right dominant subjects (left, 12; right, 5). The results are inconsistent with previous studies on the incidence of constructional apraxia. In addition, we found activation in regions that were not previously reported in the literature of constructional apraxia: they are the ventral premotor area and posterior part of inferior temporal sulcus.

Mirror-image discrimination in the literate brain: a causal role for the left occpitotemporal cortex.

Previous studies show that the primate and human visual system automatically generates a common and invariant representation from a visual object image and its mirror reflection. For humans, however, this mirror-image generalization seems to be partially suppressed through literacy acquisition, since literate adults have greater difficulty in recognizing mirror images of letters than those of other visual objects. At the neural level, such category-specific effect on mirror-image processing has been associated with the left occpitotemporal cortex (L-OTC), but it remains unclear whether the apparent "inhibition" on mirror letters is mediated by suppressing mirror-image representations covertly generated from normal letter stimuli. Using transcranial magnetic stimulation (TMS), we examined how transient disruption of the L-OTC affects mirror-image recognition during a same-different judgment task, while varying the semantic category (letters and non-letter objects), identity (same or different), and orientation (same or mirror-reversed) of the first and second stimuli. We found that magnetic stimulation of the L-OTC produced a significant delay in mirror-image recognition for letter-strings but not for other objects. By contrast, this category specific impact was not observed when TMS was applied to other control sites, including the right homologous area and vertex. These results thus demonstrate a causal link between the L-OTC and mirror-image discrimination in literate people. We further suggest that left-right sensitivity for letters is not achieved by a local inhibitory mechanism in the L-OTC but probably relies on the inter-regional coupling with other orientation-sensitive occipito-parietal regions.

Hierarchical functional connectivity between the core language system and the working memory system.

Language processing inevitably involves working memory (WM) operations, especially for sentences with complex syntactic structures. Evidence has been provided for a neuroanatomical segregation between core syntactic processes and WM, but the dynamic relation between these systems still has to be explored. In the present functional magnetic resonance imaging (fMRI) study, we investigated the network dynamics of regions involved in WM operations which support sentence processing during reading, comparing a set of dynamic causal models (DCM) with different assumptions about the underlying connectional architecture. The DCMs incorporated the core language processing regions (pars opercularis and middle temporal gyrus), WM related regions (inferior frontal sulcus and intraparietal sulcus), and visual word form area (fusiform gyrus). The results indicate a processing hierarchy from the visual to WM to core language systems, and moreover, a clear increase of connectivity between WM regions and language regions as the processing load increases for syntactically complex sentences.

An approach to separating the levels of hierarchical structure building in language and mathematics.

We aimed to dissociate two levels of hierarchical structure building in language and mathematics, namely 'first-level' (the build-up of hierarchical structure with externally given elements) and 'second-level' (the build-up of hierarchical structure with internally represented elements produced by first-level processes). Using functional magnetic resonance imaging, we investigated these processes in three domains: sentence comprehension, arithmetic calculation (using Reverse Polish notation, which gives two operands followed by an operator) and a working memory control task. All tasks required the build-up of hierarchical structures at the first- and second-level, resulting in a similar computational hierarchy across language and mathematics, as well as in a working memory control task. Using a novel method that estimates the difference in the integration cost for conditions of different trial durations, we found an anterior-to-posterior functional organization in the prefrontal cortex, according to the level of hierarchy. Common to all domains, the ventral premotor cortex (PMv) supports first-level hierarchy building, while the dorsal pars opercularis (POd) subserves second-level hierarchy building, with lower activation for language compared with the other two tasks. These results suggest that the POd and the PMv support domain-general mechanisms for hierarchical structure building, with the POd being uniquely efficient for language.