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.

Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia.

Spasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.

On-Surface Synthesis of a π-Extended Diaza[8]circulene.

Heterocyclic [8]circulenes are an important class of polycyclic aromatic hydrocarbon molecules because of their unique structural properties and promising applications. However, the synthesis of heterocyclic [8]circulenes is still limited and thus is an important synthetic challenge. Here we describe the first example of a π-extended diaza[8]circulene surrounded by and fused with six hexagons and two pentagons, which was successfully synthesized only by a combined in-solution and on-surface synthetic strategy. State-of-the-art scanning tunneling microscopy with a CO-functionalized tip and density functional theory calculations revealed its planar conformation and unique electronic structure.

Left Amygdala Regulates the Cerebral Reading Network During Fast Emotion Word Processing.

Emotion words constitute a special class of verbal stimuli which can quickly activate the limbic system outside the left-hemisphere language network. Such fast response to emotion words may arise independently of the left occipitotemporal area involved in visual word-form analysis and rely on a distinct amygdala-dependent emotion circuit involved in fearful face processing. Using a hemifield priming paradigm with fMRI, we explored how the left and right amygdala systems interact with the reading network during emotion word processing. On each trial, participants viewed a centrally presented target which was preceded by a masked prime flashed either to the left or right visual field. Primes and targets, each denoting negative or positive nouns, could be either affectively congruent or incongruent with each other. We observed that affective congruency produced parallel changes in neural priming between the left frontal and parietotemporal regions and the bilateral amygdala. However, we also found that the left, but not right, amygdala exhibited significant change in functional connectivity with the neural components of reading as a function of affective congruency. Collectively, these results suggest that emotion words activate the bilateral amygdala during early stages of emotion word processing, whereas only the left amygdala exerts a long-distance regulatory influence over the reading network via its strong within-hemisphere connectivity.

Synthesis of carbonyl-bridged dibenzofulvalenes and related compounds by rhodium-catalyzed stitching reaction.

Various carbonyl-bridged dibenzofulvalenes were synthesized by a sequence of rhodium-catalyzed stitching reaction and post-functionalization, and their optical and electronic properties could be tuned by changing the terminal substituents. The present stitching reaction also allowed for facile synthesis of dibenzofulvalenes having C, Si, Ge, S, and P as the bridging elements.

Functionalization of Azapentabenzocorannulenes by Fivefold C-H Borylation and Cross-Coupling Arylation: Application to Columnar Liquid-Crystalline Materials.

Herein, the one-shot fivefold functionalization of azapentabenzocorannulenes by an iridium-catalyzed fivefold C-H borylation reaction that exhibits excellent regioselectivity is reported. The borylated product can be used as a versatile synthetic intermediate for further derivatization via Suzuki-Miyaura cross-coupling reactions. This fivefold borylation/arylation sequence was employed to synthesize liquid-crystalline azapentabenzocorannulenes with five 3,4,5-trialkoxyphenyl groups, which assemble into 1D hexagonal columnar structures over a wide temperature range. The present method expands the variety and utility of azapentabenzocorannulenes as promising π-conjugated cores.

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.

Phonological memory in sign language relies on the visuomotor neural system outside the left hemisphere language network.

Sign language is an essential medium for everyday social interaction for deaf people and plays a critical role in verbal learning. In particular, language development in those people should heavily rely on the verbal short-term memory (STM) via sign language. Most previous studies compared neural activations during signed language processing in deaf signers and those during spoken language processing in hearing speakers. For sign language users, it thus remains unclear how visuospatial inputs are converted into the verbal STM operating in the left-hemisphere language network. Using functional magnetic resonance imaging, the present study investigated neural activation while bilinguals of spoken and signed language were engaged in a sequence memory span task. On each trial, participants viewed a nonsense syllable sequence presented either as written letters or as fingerspelling (4-7 syllables in length) and then held the syllable sequence for 12 s. Behavioral analysis revealed that participants relied on phonological memory while holding verbal information regardless of the type of input modality. At the neural level, this maintenance stage broadly activated the left-hemisphere language network, including the inferior frontal gyrus, supplementary motor area, superior temporal gyrus and inferior parietal lobule, for both letter and fingerspelling conditions. Interestingly, while most participants reported that they relied on phonological memory during maintenance, direct comparisons between letters and fingers revealed strikingly different patterns of neural activation during the same period. Namely, the effortful maintenance of fingerspelling inputs relative to letter inputs activated the left superior parietal lobule and dorsal premotor area, i.e., brain regions known to play a role in visuomotor analysis of hand/arm movements. These findings suggest that the dorsal visuomotor neural system subserves verbal learning via sign language by relaying gestural inputs to the classical left-hemisphere language network.

Remembering my friends: Medial prefrontal and hippocampal contributions to the self-reference effect on face memories in a social context.

Memories associated with the self are remembered more accurately than those associated with others. The memory enhancement related to the self is known as the self-reference effect (SRE). However, little is known regarding the neural mechanisms underlying the SRE in a social context modulated by social relationships. In the present fMRI study, we investigated encoding-related activation of face memories encoded with the self-referential process in a social context that was manipulated by imagining a person-to-person relationship. Healthy young adults participated in the present study. During encoding, participants encoded unfamiliar target faces by imagining a future friendship with themselves (Self), their friends (Friend), or strangers (Other). During retrieval, participants were presented with target and distracter faces one by one, and they judged whether each face had been previously learned. In the behavioral results, target faces encoded in the Self condition were remembered more accurately than those encoded in the Other condition. fMRI results demonstrated that encoding-related activation in the medial prefrontal cortex (mPFC) was significantly greater in the Self condition than in the Friend or Other conditions. In addition, the generalized psycho-physiological interaction (gPPI) analysis showed that functional connectivity between activation in the hippocampus and the cortical midline structures (CMSs), including the mPFC and precuneus, was significant in the Self but not in the Other condition. These findings suggest that the SRE in a social context could be involved in the interaction between the CMS regions, which are related to the self-referential process, and the hippocampus related to the memory process. Hum Brain Mapp 38:4256-4269, 2017. © 2017 Wiley Periodicals, Inc.

Stimulus-driven changes in the direction of neural priming during visual word recognition.

Visual object recognition is generally known to be facilitated when targets are preceded by the same or relevant stimuli. For written words, however, the beneficial effect of priming can be reversed when primes and targets share initial syllables (e.g., "boca" and "bono"). Using fMRI, the present study explored neuroanatomical correlates of this negative syllabic priming. In each trial, participants made semantic judgment about a centrally presented target, which was preceded by a masked prime flashed either to the left or right visual field. We observed that the inhibitory priming during reading was associated with a left-lateralized effect of repetition enhancement in the inferior frontal gyrus (IFG), rather than repetition suppression in the ventral visual region previously associated with facilitatory behavioral priming. We further performed a second fMRI experiment using a classical whole-word repetition priming paradigm with the same hemifield procedure and task instruction, and obtained well-known effects of repetition suppression in the left occipito-temporal cortex. These results therefore suggest that the left IFG constitutes a fast word processing system distinct from the posterior visual word-form system and that the directions of repetition effects can change with intrinsic properties of stimuli even when participants' cognitive and attentional states are kept constant.

Adaptation of the human visual system to the statistics of letters and line configurations.

By adulthood, literate humans have been exposed to millions of visual scenes and pages of text. Does the human visual system become attuned to the statistics of its inputs? Using functional magnetic resonance imaging, we examined whether the brain responses to line configurations are proportional to their natural-scene frequency. To further distinguish prior cortical competence from adaptation induced by learning to read, we manipulated whether the selected configurations formed letters and whether they were presented on the horizontal meridian, the familiar location where words usually appear, or on the vertical meridian. While no natural-scene frequency effect was observed, we observed letter-status and letter frequency effects on bilateral occipital activation, mainly for horizontal stimuli. The findings suggest a reorganization of the visual pathway resulting from reading acquisition under genetic and connectional constraints. Even early retinotopic areas showed a stronger response to letters than to rotated versions of the same shapes, suggesting an early visual tuning to large visual features such as letters.

Timing the impact of literacy on visual processing.

Learning to read requires the acquisition of an efficient visual procedure for quickly recognizing fine print. Thus, reading practice could induce a perceptual learning effect in early vision. Using functional magnetic resonance imaging (fMRI) in literate and illiterate adults, we previously demonstrated an impact of reading acquisition on both high- and low-level occipitotemporal visual areas, but could not resolve the time course of these effects. To clarify whether literacy affects early vs. late stages of visual processing, we measured event-related potentials to various categories of visual stimuli in healthy adults with variable levels of literacy, including completely illiterate subjects, early-schooled literate subjects, and subjects who learned to read in adulthood (ex-illiterates). The stimuli included written letter strings forming pseudowords, on which literacy is expected to have a major impact, as well as faces, houses, tools, checkerboards, and false fonts. To evaluate the precision with which these stimuli were encoded, we studied repetition effects by presenting the stimuli in pairs composed of repeated, mirrored, or unrelated pictures from the same category. The results indicate that reading ability is correlated with a broad enhancement of early visual processing, including increased repetition suppression, suggesting better exemplar discrimination, and increased mirror discrimination, as early as ∼ 100-150 ms in the left occipitotemporal region. These effects were found with letter strings and false fonts, but also were partially generalized to other visual categories. Thus, learning to read affects the magnitude, precision, and invariance of early visual processing.

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.

Eating tools in hand activate the brain systems for eating action: a transcranial magnetic stimulation study.

There is increasing neuroimaging evidence suggesting that visually presented tools automatically activate the human sensorimotor system coding learned motor actions relevant to the visual stimuli. Such crossmodal activation may reflect a general functional property of the human motor memory and thus can be operating in other, non-limb effector organs, such as the orofacial system involved in eating. In the present study, we predicted that somatosensory signals produced by eating tools in hand covertly activate the neuromuscular systems involved in eating action. In Experiments 1 and 2, we measured motor evoked response (MEP) of the masseter muscle in normal humans to examine the possible impact of tools in hand (chopsticks and scissors) on the neuromuscular systems during the observation of food stimuli. We found that eating tools (chopsticks) enhanced the masseter MEPs more greatly than other tools (scissors) during the visual recognition of food, although this covert change in motor excitability was not detectable at the behavioral level. In Experiment 3, we further observed that chopsticks overall increased MEPs more greatly than scissors and this tool-driven increase of MEPs was greater when participants viewed food stimuli than when they viewed non-food stimuli. A joint analysis of the three experiments confirmed a significant impact of eating tools on the masseter MEPs during food recognition. Taken together, these results suggest that eating tools in hand exert a category-specific impact on the neuromuscular system for eating.

Literacy breaks mirror invariance for visual stimuli: a behavioral study with adult illiterates.

The ability to recognize 2 mirror images as the same picture across left-right inversions exists early on in humans and other primates. In order to learn to read, however, one must discriminate the left-right orientation of letters and distinguish, for instance, b from d. We therefore reasoned that literacy may entail a loss of mirror invariance. To evaluate this hypothesis, we asked adult literates, illiterates, and ex-illiterates to perform a speeded same-different task with letter strings, false fonts, and pictures regardless of their orientation (i.e., they had to respond "same" to mirror pairs such as "iblo oldi"). Literates presented clear difficulties with mirror invariance. This "mirror cost" effect was strongest with letter strings, but crucially, it was also observed with false fonts and even with pictures. In contrast, illiterates did not present any cost for mirror pairs. Interestingly, subjects who learned to read as adults also exhibited a mirror cost, suggesting that modest reading practice, late in life, can suffice to break mirror invariance.

Universal brain systems for recognizing word shapes and handwriting gestures during reading.

Do the neural circuits for reading vary across culture? Reading of visually complex writing systems such as Chinese has been proposed to rely on areas outside the classical left-hemisphere network for alphabetic reading. Here, however, we show that, once potential confounds in cross-cultural comparisons are controlled for by presenting handwritten stimuli to both Chinese and French readers, the underlying network for visual word recognition may be more universal than previously suspected. Using functional magnetic resonance imaging in a semantic task with words written in cursive font, we demonstrate that two universal circuits, a shape recognition system (reading by eye) and a gesture recognition system (reading by hand), are similarly activated and show identical patterns of activation and repetition priming in the two language groups. These activations cover most of the brain regions previously associated with culture-specific tuning. Our results point to an extended reading network that invariably comprises the occipitotemporal visual word-form system, which is sensitive to well-formed static letter strings, and a distinct left premotor region, Exner's area, which is sensitive to the forward or backward direction with which cursive letters are dynamically presented. These findings suggest that cultural effects in reading merely modulate a fixed set of invariant macroscopic brain circuits, depending on surface features of orthographies.

Task-sensitivity of unconscious word processing in spatial neglect.

Neuropsychological studies of spatial neglect have shown that ignored visual stimuli can produce measurable behavioral changes without eliciting subjective perceptual experience. However, such non-conscious, implicit cognitive processing may not be fully automatic but rather could be influenced by the patients' voluntary behavioral control. Using a hemifield priming paradigm with two different task instructions, we studied spatial neglect patients to assess whether non-conscious processing of ignored words is modulated by behavioral task requirements. In each trial, participants named or categorized a centrally presented target following a masked prime flashed to the left or right hemifield. By delivering equally invisible stimuli to both hemifields, this design allowed rigorous testing of the impact of task instructions on non-conscious processing in neglect patients and control participants. We observed that neglect patients showed slightly different patterns of masked priming from those obtained in healthy and right-hemisphere control patients. Importantly, however, all these three groups showed strong sensitivity to task contexts during the unconscious processing of masked words. The present results provide neuropsychological evidence that robust task-sensitive neural pathways are covertly operating on weak and normally imperceptible visual stimuli even when visuospatial attention is severely compromised.

Symmetrical hemispheric priming in spatial neglect: a hyperactive left-hemisphere phenomenon?

Hemispheric rivalry models of spatial neglect suggest that the left hemisphere becomes hyperactive following right-hemisphere lesions since the two hemispheres normally exert an inhibitory influence on each other via callosal connections. Using a masked hemifield priming paradigm, we investigated whether the putative change in hemispheric balance involves other, higher-order abstract representational systems in spatial neglect. Participants consisted of 12 neglect patients with right-hemisphere damage and three groups of control participants, i.e., 12 young healthy controls, 10 age-matched healthy controls and 10 right-hemisphere patients without spatial neglect. In each trial, participants made semantic categorization about a centrally presented target word which was preceded by a masked prime flashed either to the left or right visual field. All three control groups exhibited strong left-hemisphere advantage in inhibitory syllabic priming, consistent with the known left-hemisphere dominance in lexical inhibition during reading. By contrast, neglect patients exhibited a symmetrical pattern of priming between the left and right visual fields. These results suggest that (1) the neglected hemifield can rapidly extract abstract information even from weak and normally non-perceptible visual stimuli, but that (2) the normal left hemispheric dominance in reading is absent in neglect patients probably because of the generalized hyperactivity of the left hemisphere. Our results demonstrate a covert behavioral change in spatial neglect which may reflect the altered inter-hemispheric balance in the bilateral word recognition system encompassing lexico-semantic memory.

Breaking the symmetry: mirror discrimination for single letters but not for pictures in the Visual Word Form Area.

Humans and primates can quickly recognize mirror images of previously exposed pictures. This spontaneous mirror invariance, though advantageous for visual recognition, makes it difficult to distinguish the orientation of letters (e.g. to differentiate a "b" from a "d"), and may result in classical mirror reading and writing errors in preschoolers. Mirror invariance must therefore be overcome during reading acquisition. The Visual Word Form Area (VWFA), a region in the ventral stream that develops with reading expertise, was previously shown to discriminate words from their mirror images in literate adults. Here we investigate whether this region underlies mirror-image discrimination at the most elementary level of the orthographic code, the single-letter level. Using an fMRI priming paradigm, we demonstrate that the VWFA distinguishes the left-right orientation of single letters in skilled readers, and yet exhibits mirror invariance for simple pictures of matched complexity. These results clarify how letter shapes, after reading acquisition, escape the process of mirror invariance which is a basic property of the ventral visual shape recognition pathway.