Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4+ T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4+ T cells in white matter, gray matter-infiltrated CD4+ T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4+ T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4+T cell into the gray matter to induce neuronal damage.

Mutation spectrum and genotype-phenotype correlations in 157 Korean CADASIL patients: a multicenter study.

CADASIL is an inherited disease caused by mutations in the NOTCH3 gene. We aimed to investigate the mutation and clinical spectrum, and genotype-phenotype correlations of Korean CADASIL patients. Samples from 492 clinically suspicious patients were collected from four hospitals. Sanger sequencing was performed to screen exons 2 to 25 of the NOTCH3 gene and variants of unknown significance (VUS) were analyzed using the ACMG guidelines. The medical records and MRI data were received from each hospital, for comprehensive analysis of genotype-phenotype correlations. Previously reported NOTCH3 variants were most commonly detected in exon 11 whereas exon 4 was the most common in European studies. The variants were detected equally between the EGFr domains 1-6 and 7-34, which was different from EGFr 1-6 predominant European studies. The average age-of-onset of patients with EGFr 1-6 variants were 4.81 ± 1.95 years younger than patients with EGFr 7-34 variants. Overall, it took Korean patients 51.2 ± 10 years longer to develop CADASIL in comparison to European patients. The most common mutation was p.R544C, which was associated with a later onset of stroke and a significant time-to-event curve difference. We verified four atypical phenotypes of p.R544C that had been reported in previous studies. Eight novel variants in 15 patients were detected but remained a VUS based on the ACMG criteria. This study reported a different EGFr distribution of Korean patients in comparison to European patients and its correlation with a later age-of-onset. An association between a later onset of stroke/TIA and p.R544C was observed.

Blocking of irrelevant memories by posterior alpha activity boosts memory encoding.

In our daily lives, we are confronted with a large amount of information. Because only a small fraction can be encoded in long-term memory, the brain must rely on powerful mechanisms to filter out irrelevant information. To understand the neuronal mechanisms underlying the gating of information into long-term memory, we employed a paradigm where the encoding was directed by a "Remember" or a "No-Remember" cue. We found that posterior alpha activity increased prior to the "No-Remember" stimuli, whereas it decreased prior to the "Remember" stimuli. The sources were localized in the parietal cortex included in the dorsal attention network. Subjects with a larger cue-modulation of the alpha activity had better memory for the to-be-remembered items. Interestingly, alpha activity reflecting successful inhibition following the "No-Remember" cue was observed in the frontal midline structures suggesting preparatory inhibition was mediated by anterior parts of the dorsal attention network. During the presentation of the memory items, there was more gamma activity for the "Remember" compared to the "No-Remember" items in the same regions. Importantly, the anticipatory alpha power during cue predicted the gamma power during item. Our findings suggest that top-down controlled alpha activity reflects attentional inhibition of sensory processing in the dorsal attention network, which then finally gates information to long-term memory. This gating is achieved by inhibiting the processing of visual information reflected by neuronal synchronization in the gamma band. In conclusion, the functional architecture revealed by region-specific changes in the alpha activity reflects attentional modulation which has consequences for long-term memory encoding.

Neural correlates of bridging inferences and coherence processing.

We explored the neural correlates of bridging inferences and coherence processing during story comprehension using Positron Emission Tomography (PET). Ten healthy right-handed volunteers were visually presented three types of stories (Strong Coherence, Weak Coherence, and Control) consisted of three sentences. The causal connectedness among sentences in the Strong Coherence story was strong that readers would not have to generate bridging inferences, whereas the causal antecedent of the last sentence in the Weak Coherence story was not explicitly stated so that readers should draw bridging inferences to fill the gap between sentences. It was found that the left middle temporal gyrus was activated while participants read the Weak Coherence stories. In contrast, the dorsomedial prefrontal cortex (dmPFC) and posterior cingulate cortex were activated only in the Strong Coherence condition. This suggests that the dmPFC was involved in coherence processing whereas bridging inference was mediated by the left middle temporal gyrus. It was also found that anterior temporal pole and the temporo-parietal junction mediated general semantic processing.

Early-life-trauma triggers interferon-ß resistance and neurodegeneration in a multiple sclerosis model via downregulated ß1-adrenergic signaling.

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-ß resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with ß1 adrenergic receptor antagonist. Conversely, ß1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell ß1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of ß1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.

Neural correlates of hemispatial neglect: a voxel-based SPECT study.

BACKGROUND: Despite many studies that investigated the neural correlates of hemispatial neglect (HN) with structural imaging, studies using voxel-wise analyses of functional imaging are not available. Furthermore, previous studies neither considered the neglect severity nor investigated whether there are differences in these neural correlates according to each neglect subtest. This study aimed to investigate the neural correlates of HN by correlating the total and the individual neglect score with hypoperfusion value on single photon emission computed tomography (SPECT) using voxel-wise analyses. METHODS: Forty-two patients with acute right hemisphere strokes underwent a neglect test battery consisting of 3 bisection tasks, 2 cancellation tasks and 2 copying tasks. The SPECT images were acquired in these patients and 10 age- and education-matched normal controls. RESULTS: Patients with HN, compared to those without HN, had hypoperfusion in the right middle temporal-occipital junction, inferior frontal gyrus and retrosplenial area. The total neglect score correlated with the hypoperfusion in the right middle temporal-occipital junction, fusiform gyrus, parahippocampal gyrus, inferior temporal gyrus, anterior part of the superior and middle temporal gyri, cuneus, lingual gyrus, angular gyrus, and the cerebellum. Across the neglect subtests similar correlation patterns were observed with minor variations. CONCLUSIONS: Unlike the results of previous studies showing that the critical neural correlates for HN are inferior parietal lobule or superior temporal gyrus, our study showed that the lesions that critically contribute to the neglect severity were located in the posterior parts of the middle temporal gyrus (temporal-occipital junction).

Th1-Dependent Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage.

Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is identified upon immune reconstitution in immunocompromised patients, who have previously contracted an infection of Cryptococcus neoformans (Cn). C-IRIS can be lethal but how the immune system triggers life-threatening outcomes in patients is still poorly understood. Here, we establish a mouse model for C-IRIS with Cn serotype A strain H99, which is highly virulent and the most intensively studied. C-IRIS in mice is induced by the adoptive transfer of CD4+ T cells in immunocompromised Rag1-deficient mice infected with a low inoculum of Cn. The mice with C-IRIS exhibit symptoms which mimic clinical presentations of C-IRIS. This C-IRIS model is Th1-dependent and shows host mortality. This model is characterized with minimal lung injury, but infiltration of Th1 cells in the brain. C-IRIS mice also exhibited brain swelling with resemblance to edema and upregulation of aquaporin-4, a critical protein that regulates water flux in the brain in a Th1-dependent fashion. Our C-IRIS model may be used to advance our understanding of the paradoxical inflammatory phenomenon of C-IRIS in the context of neuroinflammation.

An Isoform of the Oncogenic Splice Variant AIMP2-DX2 Detected by a Novel Monoclonal Antibody.

AIMP2-DX2, an exon 2-deleted splice variant of AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein 2), is highly expressed in lung cancer and involved in tumor progression in vivo. Oncogenic function of AIMP2-DX2 and its correlation with poor prognosis of cancer patients have been well established; however, the application of this potentially important biomarker to cancer research and diagnosis has been hampered by a lack of antibodies specific for the splice variant, possibly due to the poor immunogenicity and/or stability of AIMP2-DX2. In this study a monoclonal antibody, H5, that specifically recognizes AIMP2-DX2 and its isoforms was generated via rabbit immunization and phage display techniques, using a short peptide corresponding to the exon 1/3 junction sequence as an antigen. Furthermore, based on mutagenesis, limited cleavage, and mass spectrometry studies, it is also suggested that the endogenous isoform of AIMP2-DX2 recognized by H5 is produced by proteolytic cleavage of 33 amino acids from N-terminus and is capable of inducing cell proliferation similarly to the uncleaved protein. H5 monoclonal antibody is applicable to enzyme-linked immunosorbent assay, immunoblot, immunofluorescence, and immunohistochemistry, and expected to be a valuable tool for detecting AIMP2-DX2 with high sensitivity and specificity for research and diagnostic purposes.

Different hemispheric specializations for pitch and audioverbal working memory.

Critical times of involvement of areas important to working memory were examined both with pitch and audioverbal N-back tasks using single-pulse transcranial magnetic stimulation (TMS). TMS was administered to 12 healthy participants over dorsolateral prefrontal and inferior parietal regions in each hemisphere at four different times after stimulus onset (250, 450, 650, and 850 ms). For the pitch N-back task, interference with working memory, as evidenced by a significant increase in reaction time, was observed with TMS over the right hemisphere regions. In contrast, for the audioverbal N-back task, TMS resulted in significantly increased reaction time only for left inferior parietal TMS delivered 450 ms after stimulus onset. These results imply different hemispheric specializations for pitch and audioverbal working memory.

Strength of resting-state functional connectivity associated with performance-adjustment ability.

Erroneous behavior is usually, although not always, inhibited following a negative outcome (e.g., a penalty), although this adjusting behavior is highly varied. Here we aimed to identify brain regions associated with successful behavioral adjustment to negative feedback, and the intrinsic functional connectivity associated with individual variability in such adjustments, using combined task-based and resting-state functional magnetic resonance imaging (MRI). Functional MRI data were obtained from 28 young adults performing a visuomotor associative learning task, wherein participants learned by trial and error to make one of four key responses to each of 24 English letters. All preceding error response trials were sorted post hoc, based on whether the error response was repeated (Error-Repeated) or not (Error-Changed) for the subsequent trial with the same stimulus, and the rate of error adjustment for each individual was computed as the number of Error-Changed trials divided by all error trials. We identified two brain regions, the right dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (DLPFC), whose brain response was significantly greater for Error-Changed than Error-Repeated trials. Stronger anti-correlation between the right dACC seed and right amygdala and between the DLPFC seed and the paracentral gyrus and inferior temporal region extending to the hippocampus was associated with better adjustment ability. These results suggest that the stronger anticorrelated relationship between the error monitoring region and emotional processing and that between the executive control region with those involved in memory or default mode network reflect individual variability in error adjustment.

Internet Game Overuse Is Associated With an Alteration of Fronto-Striatal Functional Connectivity During Reward Feedback Processing.

Internet gaming disorder is associated with abnormal reward processing in the reward circuit, which is known to interact with other brain regions during feedback learning. Kim et al. (1) observed that individuals with internet game overuse (IGO) exhibit altered behavior and neural activity for non-monetary reward, but not for monetary reward. Here, we extend our analysis of IGO to the functional connectivity of the reward network. Functional MRI data were obtained during a stimulus-response association learning task from 18 young males with IGO and 20 age-matched controls, where either monetary or non-monetary rewards were given as positive feedback for a correct response. Group differences in task-dependent functional connectivity were examined for the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS), which are known for reward evaluation and hedonic response processing, respectively, using a generalized form of the psychophysiological interaction approach. For non-monetary reward processing, no differences in functional connectivity were found. In contrast, for monetary reward, connectivity of the vmPFC with the left caudate nucleus was weaker for the IGO group relative to controls, while vmPFC connectivity with the right nucleus accumbens (NAcc) was elevated. The strength of vmPFC-NAcc functional connectivity appeared to be behaviorally relevant, because individuals with stronger vmPFC-NAcc connectivity showed lower learning rates for monetary reward. In addition, the IGO group showed weaker ventral striatum functional connectivity with various brain regions, including the right ventrolateral prefrontal cortex, dorsal anterior cingulate regions, and left pallidum. Thus, for monetary reward, the IGO group exhibited stronger functional connectivity within the brain regions involved in motivational salience, whereas they showed reduced functional connectivity the widely distributed brain areas involved in learning or attention. These differences in functional connectivity of reward networks, along with related behavioral impairments of reward learning, suggest that internet gaming disorder is associated with the increased incentive salience or "wanting" of addiction disorders, and may serve as the neurobiological mechanisms underlying the impaired goal-directed behavior.

Impaired Feedback Processing for Symbolic Reward in Individuals with Internet Game Overuse.

Reward processing, which plays a critical role in adaptive behavior, is impaired in addiction disorders, which are accompanied by functional abnormalities in brain reward circuits. Internet gaming disorder, like substance addiction, is thought to be associated with impaired reward processing, but little is known about how it affects learning, especially when feedback is conveyed by less-salient motivational events. Here, using both monetary (±500 KRW) and symbolic (Chinese characters "right" or "wrong") rewards and penalties, we investigated whether behavioral performance and feedback-related neural responses are altered in Internet game overuse (IGO) group. Using functional MRI, brain responses for these two types of reward/penalty feedback were compared between young males with problems of IGO (IGOs, n = 18, mean age = 22.2 ± 2.0 years) and age-matched control subjects (Controls, n = 20, mean age = 21.2 ± 2.1) during a visuomotor association task where associations were learned between English letters and one of four responses. No group difference was found in adjustment of error responses following the penalty or in brain responses to penalty, for either monetary or symbolic penalties. The IGO individuals, however, were more likely to fail to choose the response previously reinforced by symbolic (but not monetary) reward. A whole brain two-way ANOVA analysis for reward revealed reduced activations in the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal cortex (vmPFC) in response to both reward types, suggesting impaired reward processing. However, the responses to reward in the inferior parietal region and medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO group. Unlike the control group, in the IGO group the reward response was reduced only for symbolic reward, suggesting lower attentional and value processing specific to symbolic reward. Furthermore, the more severe the Internet gaming overuse symptoms in the IGO group, the greater the activations of the ventral striatum for monetary relative to symbolic reward. These findings suggest that IGO is associated with bias toward motivationally salient reward, which would lead to poor goal-directed behavior in everyday life.

Gating of memory encoding of time-delayed cross-frequency MEG networks revealed by graph filtration based on persistent homology.

To explain gating of memory encoding, magnetoencephalography (MEG) was analyzed over multi-regional network of negative correlations between alpha band power during cue (cue-alpha) and gamma band power during item presentation (item-gamma) in Remember (R) and No-remember (NR) condition. Persistent homology with graph filtration on alpha-gamma correlation disclosed topological invariants to explain memory gating. Instruction compliance (R-hits minus NR-hits) was significantly related to negative coupling between the left superior occipital (cue-alpha) and the left dorsolateral superior frontal gyri (item-gamma) on permutation test, where the coupling was stronger in R than NR. In good memory performers (R-hits minus false alarm), the coupling was stronger in R than NR between the right posterior cingulate (cue-alpha) and the left fusiform gyri (item-gamma). Gating of memory encoding was dictated by inter-regional negative alpha-gamma coupling. Our graph filtration over MEG network revealed these inter-regional time-delayed cross-frequency connectivity serve gating of memory encoding.

Formation of visual memories controlled by gamma power phase-locked to alpha oscillations.

Neuronal oscillations provide a window for understanding the brain dynamics that organize the flow of information from sensory to memory areas. While it has been suggested that gamma power reflects feedforward processing and alpha oscillations feedback control, it remains unknown how these oscillations dynamically interact. Magnetoencephalography (MEG) data was acquired from healthy subjects who were cued to either remember or not remember presented pictures. Our analysis revealed that in anticipation of a picture to be remembered, alpha power decreased while the cross-frequency coupling between gamma power and alpha phase increased. A measure of directionality between alpha phase and gamma power predicted individual ability to encode memory: stronger control of alpha phase over gamma power was associated with better memory. These findings demonstrate that encoding of visual information is reflected by a state determined by the interaction between alpha and gamma activity.

Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection.

The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production. Administration of FL-WRS into Salmonella typhimurium-infected mice reduced the levels of bacteria and improved mouse survival, whereas its titration with the specific antibody aggravated the infection. The N-terminal 154-amino-acid eukaryote-specific peptide of WRS was sufficient to recapitulate FL-WRS activity and its interaction mode with TLR4-MD2 is now suggested. Based on these results, secretion of FL-WRS appears to work as a primary defence system against infection, acting before full activation of innate immunity.

Prediction of the clinical outcome of pediatric moyamoya disease with postoperative basal/acetazolamide stress brain perfusion SPECT after revascularization surgery.

BACKGROUND AND PURPOSE: We evaluated whether basal/acetazolamide stress brain perfusion SPECT performed after revascularization surgery can predict the further clinical outcome of patients with pediatric moyamoya disease. METHODS: A total of 77 (31 males, 46 females, age 6.6+/-3.2 years) patients with postoperative pediatric moyamoya disease who underwent basal/acetazolamide stress brain perfusion SPECT 6 to 12 months after revascularization surgery and who were followed-up >12 months after SPECT were included. Mean follow-up period after SPECT was 36+/-19 months. Sixty-two patients underwent bilateral ribbon encephaloduroarteriosynangiosis (EDAS), 14 bilateral EDAS, and 1 unilateral EDAS. Ordinal logistic regression analysis using 5 independent variables (infarction on preoperative MRI, age at the first operation, highest Suzuki stage on cerebral angiography, and regional cerebrovascular reserve on postoperative SPECT) against postoperative clinical outcomes was performed. RESULTS: Fifty-one patients had preserved reserve on postoperative SPECT and their clinical outcomes were excellent (30), good (15), fair (4), and poor (2); 26 patients had decreased reserve (excellent, 1; good, 7; fair, 14; poor, 4). On ordinal logistic regression analysis, age at the first operation (P=0.033) and reserve on postoperative SPECT (P<0.001) were statistically significant. CONCLUSIONS: Basal/acetazolamide stress brain perfusion SPECT performed at 6 to 12 months after the indirect bypass operation could predict the further clinical outcome of pediatric patients with moyamoya disease. Patients with decreased cerebrovascular reserve will have remaining neurological deficit and ischemic attacks on follow-up.

18F-FDG PET findings in frontotemporal dementia: an SPM analysis of 29 patients.

UNLABELLED: Frontotemporal dementia (FTD) is a common cause of presenile dementia. The aim of the current study was 2-fold: (a) to delineate the brain regions with reduction of glucose metabolism, and (b) to investigate the hemispheric asymmetry of glucose metabolism in FTD using (18)F-FDG PET. METHODS: We compared the regional metabolic patterns on (18)F-FDG PET images obtained from 29 patients with FTD and 11 healthy subjects using a voxel-wise analysis (statistical parametric mapping [SPM]). The hemispheric asymmetry of glucose metabolism was computed based on 2 different measures: one (AI(ROI)) by counting the (18)F-FDG activity of each hemisphere on the normalized and spatially smoothed PET images and the other (AI(SPM)) by counting the number of voxels with significant hypometabolism based on SPM results. RESULTS: Significant hypometabolism was identified in extensive prefrontal areas, cingulate gyri, anterior temporal regions, and the left inferior parietal lobule. Hypometabolism was also found in the bilateral insula and uncus, left putamen and globus pallidus, and medial thalamic structures. Frontal hypometabolism was more prominent in the left hemisphere than in the right. Twenty-six (90%) of the 29 patients with FTD had AI(ROI) values indicating significant lateralization of glucose metabolism; 18 patients had hypometabolism more severe on the left than right side, and only 8 patients had the opposite pattern. Results from AI(SPM) showed similar patterns. CONCLUSION: The voxel-wise analysis of (18)F-FDG PET images of patients with FTD revealed hypometabolism in extensive cortical regions, such as frontal and anterior temporal areas, cingulate gyri, uncus, and insula and subcortical areas, including basal ganglia (putamen and globus pallidus) and medial thalamic regions. The hemispheric asymmetry of hypometabolism (more frequently lateralized to the left) was common in patients with FTD, which may be another metabolic feature that helps to differentiate FTD from Alzheimer's disease or other causes of dementia.

Selective synthesis of functionalized, tertiary silanes by diastereoselective rearrangement-addition.

[reaction: see text] Treatment of hydroxy-substituted silyl epoxides with Grignard reagents induces a 1,2-carbon shift to reveal alpha-silyl aldehydes, which are trapped by highly diastereoselective addition reactions of the Grignard reagent. The starting epoxides are readily accessible from propargylic alcohols by regio- and diastereoselective hydrosilylation and epoxidation reactions. In addition to providing functionalized tertiary silane products, the method is shown to offer a tertiary olefin synthesis through chemo- and diastereoselective Peterson elimination of the product tertiary silane diols.

Preoperative differences of cerebral metabolism relate to the outcome of cochlear implants in congenitally deaf children.

In congenitally deaf children, chronological age is generally accepted as a critical factor that affects successful rehabilitation following cochlear implantation (CI). However, a wide variance among patients is known to exist regardless of the age at CI [Sarant, J.Z., Blamey, P.J., Dowell, R.C., Clark, G.M., Gibson, W.P., 2001. Variation in speech perception scores among children with cochlear implants. Ear Hear. 22, 18-28]. In a previous study, we reported that prelingually deaf children in the age range 5-7 years at implantation showed greatest outcome variability [Oh S.H., Kim C.S., Kang E.J., Lee D.S., Lee H.J., Chang S.O., Ahn S.H., Hwang C.H., Park H.J., Koo J.W., 2003. Speech perception after cochlear implantation over a 4-year time period. Acta Otolaryngol. 123, 148-153]. Eleven children who underwent CI between the age of 5 and 7 1/2 years were subdivided into a good (above 65%: GOOD) and a poor (below 45%: POOR) group based on the performance in a speech perception test given 2 years after CI. The preoperative (18)F-FDG-PET (F-18 fluorodeoxyglucose positron emission tomography) images were compared between the two groups in order to examine if regional glucose metabolic difference preexisted before the CI surgery. In the GOOD group, metabolic activity was greater in diverse fronto-parietal regions compared to the POOR group. In the POOR group, the regions related to the ventral visual pathway showed greater metabolic activity relative to the GOOD group. These findings suggest that the deaf children who had developed greater executive and visuospatial functions subserved by the prefrontal and parietal cortices might be successful in auditory language learning after CI. On the contrary, greater dependency on the visual function subserved by the occipito-temporal region due to auditory deprivation may interfere with acquisition of auditory language after CI.

Brain networks engaged in audiovisual integration during speech perception revealed by persistent homology-based network filtration.

The human brain naturally integrates audiovisual information to improve speech perception. However, in noisy environments, understanding speech is difficult and may require much effort. Although the brain network is supposed to be engaged in speech perception, it is unclear how speech-related brain regions are connected during natural bimodal audiovisual or unimodal speech perception with counterpart irrelevant noise. To investigate the topological changes of speech-related brain networks at all possible thresholds, we used a persistent homological framework through hierarchical clustering, such as single linkage distance, to analyze the connected component of the functional network during speech perception using functional magnetic resonance imaging. For speech perception, bimodal (audio-visual speech cue) or unimodal speech cues with counterpart irrelevant noise (auditory white-noise or visual gum-chewing) were delivered to 15 subjects. In terms of positive relationship, similar connected components were observed in bimodal and unimodal speech conditions during filtration. However, during speech perception by congruent audiovisual stimuli, the tighter couplings of left anterior temporal gyrus-anterior insula component and right premotor-visual components were observed than auditory or visual speech cue conditions, respectively. Interestingly, visual speech is perceived under white noise by tight negative coupling in the left inferior frontal region-right anterior cingulate, left anterior insula, and bilateral visual regions, including right middle temporal gyrus, right fusiform components. In conclusion, the speech brain network is tightly positively or negatively connected, and can reflect efficient or effortful processes during natural audiovisual integration or lip-reading, respectively, in speech perception.