Enhanced activations in the dorsal inferior frontal gyrus specifying the who, when, and what for successful building of sentence structures in a new language.

It has been argued that the principles constraining first language acquisition also constrain second language acquisition; however, neuroscientific evidence for this is scant, and even less for third and subsequent languages. We conducted fMRI experiments to evaluate this claim by focusing on the building of complex sentence structures in Kazakh, a new language for participants having acquired at least two languages. The participants performed grammaticality judgment and subject-verb matching tasks with spoken sentences. We divided the participants into two groups based on the performance levels attained in one of the experimental tasks: High in Group I and Low in Group II. A direct comparison of the two groups, which examined those participants who parsed the structures, indicated significantly stronger activations for Group I in the dorsal left inferior frontal gyrus (L. IFG). Focusing on Group I, we tested the contrast between the initial and final phases in our testing, which examined when the structures were parsed, as well as the contrast which examined what structures were parsed. These analyses further demonstrated focal activations in the dorsal L. IFG alone. Among the individual participants, stronger activation in the dorsal L. IFG, measured during the sentence presentations, predicted higher accuracy rates and shorter response times for executing the tasks that followed. These results cannot be explained by task difficulty or memory loads, and they, instead, indicate a critical and consistent role of the dorsal L. IFG during the initial to intermediate stages of grammar acquisition in a new target language. Such functional specificity of the dorsal L. IFG provides neuroscientific evidence consistent with the claims made by the Cumulative-Enhancement model in investigating language acquisition beyond target second and third languages.

[Coniin, in Five Little Pigs].

In this manuscript, I provide some insights into the novel Five Little Pigs (US title: Murder in Retrospect) by Agatha Christie, and overview the neurotoxin coniine that plays an essential role in that story. Coniine is a nicotinic acetylcholine receptor antagonist, and induces a slowly spreading effect of paralysis by acting directly on the peripheral nervous system. This agent has been used as a poison for thousands of years; indeed, the philosophical text Phaedo describes that coniine was used to put Socrates to death. Based on this background, Christie's views on human nature and her creative powers are also discussed.

Differential networks for processing structural dependencies in human language: linguistic capacity vs. memory-based ordering.

Surface linear (left-to-right) arrangements of human languages are actually an amalgam of the core language system and systems that are not inherently related to language. It has been widely recognized that an unbounded array of hierarchically structured linguistic expressions is generated by the simplest combinatorial operation "Merge," and the notion of Merge-generability has been proposed as a key feature that characterizes structural dependencies among linguistic elements. Here we tested Merge-generable dependencies by using a Subject-Predicate matching task, which required both linguistic capacity and short-term memory. We used three types of dependency: Nesting, Crossing, and Grouping as the control. The Nesting dependency is totally Merge-generable, while the Crossing dependency requires some additional processes for memory-based ordering. In order to identify the regions employed for these two dependencies, we directly compared cortical responses to the sentence stimuli (with noun phrases and an adverb as the first half of stimuli, and with verbs as the latter) using functional magnetic resonance imaging (fMRI), and the following results were obtained. First, for the Nesting - Crossing contrast, significant activations were observed in the bilateral lateral premotor cortices (LPMCs) and inferior frontal gyri, left middle temporal gyrus, and bilateral angular/supramarginal gyri, indicating engagement of the syntax-related networks. In contrast, the Crossing - Nesting contrast showed focal activations in the left fusiform gyrus, lingual gyrus, and middle occipital gyrus (L. FG/LG/MOG). Secondly, for the first half of the Nesting stimuli, signal changes in the bilateral LPMCs were well fitted with the estimates of computational costs to search the workspace and to select items (Σ operations). Moreover, for the latter half of the Crossing stimuli, the signal changes in the L. FG/LG/MOG were differentially fitted with the estimates of loads related to the ordering of elements/words (numbers of Ordering). Thirdly, these fitting models were by far more likely than the exchanged estimates between bilateral LPMCs and L. FG/LG/MOG, confirming a double dissociation for primary processes with Σ and Ordering. In conclusion, these results indicate that separate cortical networks are differentially employed, and their careful elucidation will provide further insights and challenges.

Diffuse glioma-induced structural reorganization in close association with preexisting syntax-related networks.

Glioma in the left frontal cortex has been reported to cause agrammatic comprehension and induce global functional connectivity alterations within the syntax-related networks. However, it remains unclear to what extent the structural reorganization is affected by preexisting syntax-related networks. We examined 28 patients with a diffuse glioma in the left hemisphere and 23 healthy participants. Syntactic abilities were assessed by a picture-sentence matching task with various sentence types. The lesion responsible for agrammatic comprehension was identified by region-of-interest-based lesion-symptom mapping (RLSM). Cortical structural alterations were examined by surface-based morphometry (SBM), in which the cortical thickness and fractal dimension were measured with three-dimensional magnetic resonance imaging (MRI). Fiber tracking on the human population-averaged diffusion MRI template was performed to examine whether the cortical structural alterations were associated with the syntax-related networks. The RLSM revealed associations between agrammatic comprehension and a glioma in the posterior limb of the left internal capsule. The SBM demonstrated that decreased cortical thickness and/or increased complexity of the right posterior insula were associated not only with agrammatic comprehension of the patients but also with the syntactic abilities of healthy participants. The fiber tracking revealed that the route between these two regions was anatomically integrated into the preexisting syntax-related networks previously identified. These results suggest a potential association between agrammatic comprehension in patients with diffuse glioma and structural variations in specific tracts and cortical regions, which may be closely related to the syntax-related networks.

[Brain Activations during Retrieval of Colors Based on the Context of Cartoons].

The color center exists in the bilateral fusiform gyrus, but it is unknown whether this region also functions when one retrieves color information through the context of a story. To compare the effects of presentation condition/order between color and monochrome on activations in the color center, we used high-quality cartoons with a full story. We hypothesize that retrieval of colors based on the context can be much more than color retrieval through object vision. The participants performed two sets of an empathy task while their brain activations were quantified by functional magnetic resonance imaging. While color-selective activations were observed in the bilateral fusiform gyrus, habituation effects were observed only under the condition in which unnatural inverted colors were used. We confirmed that the responses of these regions to cartoons in monochrome were at the control level of color-bars even for second-half scanning runs. Moreover, when a full story cartoon on one page was presented first in monochrome, strong activations were elicited in the bilateral fusiform gyrus, which demonstrated an interaction effect similar to that of the degree of empathy. These results indicate that colors were retrieved in the brain based on the context of a cartoon. (Received 5 September, 2022; Accepted 7 November, 2022; Published 1 February, 2023).

[Main Man, Rain Man].

The titular character of the movie Rain Man is an autistic savant, and the movie centers on his relationship with his non-autistic but selfish brother. Particularly memorable scenes involve the brothers' travels; they initially lacked empathy and understanding toward each other, but they learn and expand their relationship as they spend time together. In this manuscript, I provide examples of truly amazing visual and mathematic abilities among some high-functioning autistic savants, and I introduce several hypotheses regarding the mechanisms that may underlie autism spectrum disorder, from a neuroscience perspective. The significance of these hypotheses and the current research directions are also discussed.

[The Literacy of Scientific Research and Presentation].

When presenting the results of scientific research in English as a second language, a scientist must prepare effective slides and a manuscript in its final form. Moreover, precise pronunciation and diction in English is requisite to success, and potential exchanges in the question-and-answer session should be anticipated and, if possible, rehearsed. In order to achieve these goals, a sense of aesthetics is helpful, because creative powers are integral to both the arts and sciences. For example, composition in slides can be learned by studying pictures, and phonological awareness can be strengthened by listening to music or by playing an instrument.

Music-experience-related and musical-error-dependent activations in the brain.

Although music is one of human-unique traits such as language, its neural basis for cortical organization has not been well understood. In the present functional magnetic resonance imaging study, we tested an error-detection task with different types of musical error (pitch, tempo, stress, and articulation conditions) and examined three groups of secondary school students having different levels of music experience. First, we observed distinct activation patterns under these music conditions, such that specific activations under the pitch condition were consistently replicated for all tested groups in the auditory areas, as well as in the left language areas under the articulation condition. Second, music-experience-related activations were observed in multiple regions, including the right sensorimotor area under the pitch condition, as well as in the right premotor cortex under the articulation condition. Indeed, the right homologs of the language areas were specifically activated under the stress and articulation conditions. Third, activations specific to the group with the highest proficiency in music were observed under the tempo condition mostly in the right regions. These results demonstrate the existence of music-related signatures in the brain activations, including both universal and experience-related mechanisms.

[The Pathography and Art of Beethoven].

The musician Ludwig van Beethoven suffered from hearing impairment and abdominal pain beginning in his mid-twenties. Lead intoxication can cause both of neural symptoms and digestive disorders. Lead was often present in poor-quality wines at that period, and thus Beethoven could have ingested a large amount of lead through daily wine consumption. His auditory processing disorder was merely a deficit in the lower level bottom-up processing of musical sounds or voice inputs, and probably did not affect higher level top-down processing, such as the representation of auditory imagery and composition.

Paper Notebooks vs. Mobile Devices: Brain Activation Differences During Memory Retrieval.

It remains to be determined how different inputs for memory-encoding, such as the use of paper notebooks or mobile devices, affect retrieval processes. We compared three groups of participants who read dialogues on personal schedules and wrote down the scheduled appointments on a calendar using a paper notebook (Note), an electronic tablet (Tablet), or a smartphone (Phone). After the retention period for an hour including an interference task, we tested recognition memory of those appointments with visually presented questions in a retrieval task, while scanned with functional magnetic resonance imaging. We obtained three major results. First, the duration of writing down schedules was significantly shorter for the Note group than the Tablet and Phone groups, and accuracy was much higher for the Note group in easier (i.e., more straightforward) questions. Because the input methods were equated as much as possible between the Note and Tablet groups, these results indicate that the cognitive processes for the Note group were deeper and more solid. Second, brain activations for all participants during the retrieval phase were localized in the bilateral hippocampus, precuneus, visual cortices, and language-related frontal regions, confirming the involvement of verbalized memory retrieval processes for appointments. Third, activations in these regions were significantly higher for the Note group than those for the Tablet and Phone groups. These enhanced activations for the Note group could not be explained by general cognitive loads or task difficulty, because overall task performances were similar among the groups. The significant superiority in both accuracy and activations for the Note group suggested that the use of a paper notebook promoted the acquisition of rich encoding information and/or spatial information of real papers and that this information could be utilized as effective retrieval clues, leading to higher activations in these specific regions.

Enhanced activations in syntax-related regions for multilinguals while acquiring a new language.

The neuroscientific foundation of multilingualism, a unique cognitive capacity, necessitates further elucidation. We conducted an fMRI experiment to evaluate the acquisition of syntactic features in a new language (Kazakh) for multilinguals and bilinguals. Results showed that the multilinguals who were more proficient in their second/third languages needed fewer task trials to acquire Kazakh phonology. Regarding group differences, the reduction in response times during the initial exposure to Kazakh were significantly larger for the multilinguals than the bilinguals. For the multilinguals, activations in the bilateral frontal/temporal regions were maintained at a higher level than the initial level during subsequent new grammar conditions. For the bilinguals, activations in the basal ganglia/thalamus and cerebellum decreased to the initial level each time. Direct group comparisons showed significantly enhanced activations for the multilinguals in the left ventral inferior frontal gyrus. These results indicate that both syntax-related and domain-general brain networks were more enhanced for the multilinguals. We also unexpectedly observed significant activations in the visual areas for the multilinguals, implying the use of visual representation even when listening to speech sounds alone. Because the multilinguals were able to successfully utilize acquired knowledge in an accumulated manner, the results support the cumulative-enhancement model of language acquisition.

Modality-Dependent Brain Activation Changes Induced by Acquiring a Second Language Abroad.

The dynamic nature of cortical activation changes during language acquisition, including second-language learning, has not been fully elucidated. In this study, we administered two sets of reading and listening tests (Pre and Post) to participants who had begun to learn Japanese abroad. The two sets were separated by an interval of about 2 months of Japanese language training. We compared the results of longitudinal functional MRI experiments between the two time-points and obtained the following major findings. First, the left-dominant language areas, as well as bilateral visual and auditory areas, were activated, demonstrating the synergistic effects of multiple modalities. There was also significant activation in the bilateral hippocampi, indicating the expected involvement of memory-related processes. Second, consistent with the behavioral improvements from Pre to Post, the brain activations decreased in the left inferior and middle frontal gyri during the listening tests, as well as in the visual areas (the bilateral inferior and superior parietal lobules, and left inferior and middle occipital gyri) during the reading tests, while activations in the right superior and middle temporal gyri increased during the listening tests. These modality-dependent activation changes could not be explained by domain-general cognitive factors, such as habituation or familiarization, because we used completely different test sets for Pre and Post. Third, the posterior hippocampus showed a main effect of the hemisphere, whereas the anterior hippocampus showed a significant main effect of the event (i.e., specific to first listening events), reflecting initial encoding of auditory information alone. In summary, activation changes from Pre to Post indicate functional changes in modality-dependent networks over a short period of staying abroad, which would enable effective acquisition of a second language.

[Multilingualism and the Development of the Brain].

Multilingualism is merely a parametric variation in the faculty of natural language, and it is possible to simultaneously acquire multiple languages, including dialects, at any age. While acquisition of a native language, which occurs in synchrony with development of the brain, is a multiple-step process, second language acquisition is continuous. Here, we introduce the Cumulative-Enhancement model, which states that acquisition of one additional language is beneficial for the subsequent acquisition of another. We further discuss how syntax-related networks, including multiple language areas in the brain, become functional during the course of language acquisition.

[Brain Activations Reflecting Mental States Induced by the Context of Cartoons].

Although context can be presumed to exert effects on both language and visual information processing, the relevant brain regions have not been elucidated. In the present study, we used silent manga to focus on mental states induced by visual stimuli alone. When participants read manga on a double-page spread with preserved context, significant activation was observed in the bilateral visual cortex and cerebellum. Moreover, the activated region corresponded to lesions associated with hemispatial neglect, when this condition was directly compared with a single-page presentation that impaired context. These results indicate that higher-order visual information processing is enhanced by context.

Differential Effects of a Left Frontal Glioma on the Cortical Thickness and Complexity of Both Hemispheres.

Glioma is a type of brain tumor that infiltrates and compresses the brain as it grows. Focal gliomas affect functional connectivity both in the local region of the lesion and the global network of the brain. Any anatomical changes associated with a glioma should thus be clarified. We examined the cortical structures of 15 patients with a glioma in the left lateral frontal cortex and compared them with those of 15 healthy controls by surface-based morphometry. Two regional parameters were measured with 3D-MRI: the cortical thickness (CT) and cortical fractal dimension (FD). The FD serves as an index of the topological complexity of a local cortical surface. Our comparative analyses of these parameters revealed that the left frontal gliomas had global effects on the cortical structures of both hemispheres. The structural changes in the right hemisphere were mainly characterized by a decrease in CT and mild concomitant decrease in FD, whereas those in the peripheral regions of the glioma (left hemisphere) were mainly characterized by a decrease in FD with relative preservation of CT. These differences were found irrespective of tumor volume, location, or grade. These results elucidate the structural effects of gliomas, which extend to the distant contralateral regions.

Task-Induced Functional Connectivity of the Syntax-Related Networks for Patients with a Cortical Glioma.

Analysis of the functional connectivity has enabled understanding of the cortical networks. In the present study, we used a picture-sentence matching task to introduce syntactically harder conditions, and clarified 3 major points. First, patients with a glioma in the lateral premotor cortex/inferior frontal gyrus or in other cortical regions showed much weaker activations than controls, especially in the left inferior frontal gyrus. Moreover, the error rates under the harder conditions were much higher for these patients. Secondly, syntactic loads induced selective connectivity with enhancement and suppression, consistently for both patients and controls. More specifically, the local connectivity was enhanced among the 3 syntax-related networks within the left frontal cortex, while the global connectivity of both dorsal and ventral pathways was suppressed. In addition, the exact reproducibility of r-values across the control and patient groups was remarkable, since under easier conditions alone, connectivity patterns for the patients were completely unmatched with those for the controls. Thirdly, we found an additional syntax-related network, further confirming the intergroup similarity of task-induced functional connectivity. These results indicate that functional connectivity of agrammatic patients is mostly preserved regardless of a glioma, and that the connectivity can change dynamically and systematically according to syntactic loads.

[The Last Lecture of Professor Masao Ito: The Cerebellum and Cerebrum].

Comment Professor Masao Ito's last lecture, delivered at the University of Tokyo Faculty of Medicine on March 7, 1989, is reproduced here in an abridged form. Its original title was "the Cerebellum and Cerebrum," and this lecture was a real masterpiece, full of insights and suggestions on brain functions, together with humorous phrases here and there. When I tried to reproduce this lecture by using all figures at that time, just one week after Professor Ito passed away, I was struck by his foresight even after thirty years. I deeply appreciate his family's permission for the reproduction.

Merge-Generability as the Key Concept of Human Language: Evidence From Neuroscience.

Ever since the inception of generative linguistics, various dependency patterns have been widely discussed in the literature, particularly as they pertain to the hierarchy based on "weak generation" - the so-called Chomsky Hierarchy. However, humans can make any possible dependency patterns by using artificial means on a sequence of symbols (e.g., computer programing). The differences between sentences in human language and general symbol sequences have been routinely observed, but the question as to why such differences exist has barely been raised. Here, we address this problem and propose a theoretical explanation in terms of a new concept of "Merge-generability," that is, whether the structural basis for a given dependency is provided by the fundamental operation Merge. In our functional magnetic resonance imaging (fMRI) study, we tested the judgments of noun phrase (NP)-predicate (Pred) pairings in sentences of Japanese, an SOV language that allows natural, unbounded nesting configurations. We further introduced two pseudo-adverbs, which artificially force dependencies that do not conform to structures generated by Merge, i.e., non-Merge-generable; these adverbs enable us to manipulate Merge-generability (Natural or Artificial). By employing this novel paradigm, we obtained the following results. Firstly, the behavioral data clearly showed that an NP-Pred matching task became more demanding under the Artificial conditions than under the Natural conditions, reflecting cognitive loads that could be covaried with the increased number of words. Secondly, localized activation in the left frontal cortex, as well as in the left middle temporal gyrus and angular gyrus, was observed for the [Natural - Artificial] contrast, indicating specialization of these left regions in syntactic processing. Any activation due to task difficulty was completely excluded from activations in these regions, because the Natural conditions were always easier than the Artificial ones. And finally, the [Artificial - Natural] contrast resulted in the dorsal portion of the left frontal cortex, together with wide-spread regions required for general cognitive demands. These results indicate that Merge-generable sentences are processed in these specific regions in contrast to non-Merge-generable sentences, demonstrating that Merge is indeed a fundamental operation, which comes into play especially under the Natural conditions.

[Lateralization of the Frontal Association Cortex: Syntax-related Networks].

The left inferior frontal gyrus, a part of the left frontal association cortex, is known to be involved in syntactic processing. Recently, we identified three syntax-related networks, which included each of the three regions of the left frontal association cortex. Moreover, patients with agrammatic comprehension caused by damage to the left association cortex showed changes in functional connectivity in the entire syntax-related network. These findings suggest that the left frontal association cortex is at the core of syntax-related networks.