Mutant Tof11 alleles are highly accumulated in early planting-adaptable Japanese summer type soybeans.

To avoid crop failure because of climate change, soybean (Glycine max (L.) Merrill) cultivars adaptable to early planting are required in western Japan. Because current Japanese cultivars may not be adaptable, genetic resources with high early-planting adaptability, and their genetic information must be developed. In the present study, summer type (ST) soybeans developed for early planting were used as plant materials. We examined their phenological characteristics and short reproductive period as an indicator of early planting adaptability and performed genetic studies. Biparental quantitative trait loci (QTL) analysis of a representative ST cultivar revealed a principal QTL for the reproductive period duration on chromosome 11. The results of resequencing analysis suggested that circadian clock-related Tof11 (soybean orthologue of PRR3) is a candidate QTL. Additionally, all 25 early planting-adaptable germplasms evaluated in this study possessed mutant alleles in Tof11, whereas 15 conventional cultivars only had wild-type alleles. These results suggest that mutant alleles in Tof11 are important genetic factors in the high adaptability to early planting of these soybeans, and thus, these alleles were acquired and accumulated in the ST soybean population.

Construction of a high-density linkage map and graphical representation of the arrangement of transcriptome-based unigene markers on the chromosomes of onion, Allium cepa L.

BACKGROUND: Genomic information for Allium cepa L. is limited as it is heterozygous and its genome is very large. To elucidate potential SNP markers obtained by NGS, we used a complete set of A. fistulosum L.-A. cepa monosomic addition lines (MALs) and doubled haploids (DHs). These were the parental lines of an A. cepa mapping population for transcriptome-based SNP genotyping. RESULTS: We mapped the transcriptome sequence reads from a series of A. fistulosum-A. cepa MALs onto the unigene sequence of the doubled haploid shallot A. cepa Aggregatum group (DHA) and compared the MAL genotype call for parental bunching onion and shallot transcriptome mapping data. We identified SNP sites with at least four reads on 25,462 unigenes. They were anchored on eight A. cepa chromosomes. A single SNP site was identified on 3,278 unigenes and multiple SNPs were identified on 22,184 unigenes. The chromosome marker information was made public via the web database Allium TDB ( http://alliumtdb.kazusa.or.jp/ ). To apply transcriptome based genotyping approach for genetic mapping, we gathered RNA sequence data from 96 lines of a DHA × doubled haploid bulb onion A. cepa common onion group (DHC) mapping population. After selecting co-dominant SNP sites, 16,872 SNPs were identified in 5,339 unigenes. Of these, at least two SNPs with identical genotypes were found in 1,435 unigenes. We developed a linkage map using genotype information from these unigenes. All unigene markers mapped onto the eight chromosomes and graphical genotyping was conducted based on the unigene order information. Another 2,963 unigenes were allocated onto the eight chromosomes. To confirm the accuracy of this transcriptome-based genetic linkage map, conventional PCR-based markers were used for linkage analysis. All SNP - and PCR-based markers were mapped onto the expected linkage groups and no inconsistency was found among these chromosomal locations. CONCLUSIONS: Effective transcriptome analysis with unique Allium resources successfully associated numerous chromosome markers with unigene information and a high-density A. cepa linkage map. The information on these unigene markers is valuable in genome sequencing and useful trait detection in Allium.

A QTL associated with high seed coat cracking rate of a leading Japanese soybean variety.

Seed coat cracking in soybeans [Glycine max (L). Merr.] leads to commercial and agronomic losses. The Japanese elite soybean cultivar 'Fukuyutaka' is often used as a parent for breeding, but its high rate of seed coat cracking is an obstacle to its further use in breeding programs. To establish a DNA marker-assisted selection system for seed coat cracking, genetic factors related to high rates of seed coat cracking were surveyed, and a quantitative trait locus (QTL) with a stable effect on seed coat cracking in both years of a two-year replication experiment was detected on chromosome 20. Comparison of a set of near-isogenic lines (NILs) around this locus verified that the presence of the 'Fukuyutaka' allele significantly increased seed coat cracking in the kernel. The locus is located in a genomic region spanning 3.2 Mb. Marker-assisted selection for the locus will improve the selection efficiency of 'Fukuyutaka'-derived breeding populations.

Screening and incorporation of rust resistance from Allium cepa into bunching onion (Allium fistulosum) via alien chromosome addition.

Bunching onion (Allium fistulosum L.; 2n = 16), bulb onion (Allium cepa L. Common onion group), and shallot (Allium cepa L. Aggregatum group) cultivars were inoculated with rust fungus, Puccinia allii, isolated from bunching onion. Bulb onions and shallots are highly resistant to rust, suggesting they would serve as useful resources for breeding rust resistant bunching onions. To identify the A. cepa chromosome(s) related to rust resistance, a complete set of eight A. fistulosum - shallot monosomic alien addition lines (MAALs) were inoculated with P. allii. At the seedling stage, FF+1A showed a high level of resistance in controlled-environment experiments, suggesting that the genes related to rust resistance could be located on shallot chromosome 1A. While MAAL, multi-chromosome addition line, and hypoallotriploid adult plants did not exhibit strong resistance to rust. In contrast to the high resistance of shallot, the addition line FF+1A+5A showed reproducibly high levels of rust resistance.

Static and Dynamic Functional Connectivity Alterations in Alzheimer's Disease and Neuropsychiatric Diseases.

Background: To date, numerous studies have documented various alterations in resting brain activity in Alzheimer's disease (AD) and other neuropsychiatric diseases. In particular, disease-related alterations of functional connectivity (FC) in the resting state networks (RSN) have been documented. Altered FC in RSN is useful not only for interpreting the phenotype of diseases but also for diagnosing the diseases. More recently, several studies proposed the dynamics of resting-brain activity as a useful marker for detecting altered RSNs related to AD and other diseases. Objectives: In this article, we review recent studies exploring alterations of static and dynamic functional connectivity in AD and other neuropsychiatric diseases. We then discuss how to utilize and interpret dynamics of FC for studying resting brain activity in diseases. Results: In contrast to previous studies, which focused on FC calculated using an entire fMRI scan (static FC), newer studies focused on the temporal dynamics of FC within the scan (dynamic FC) to provide more sensitive measures to characterize RSNs. However, despite the increasing popularity of dynamic FC, several statistical investigations of dynamic FC cautioned that the results obtained in commonly used analyses for dynamic FC require careful interpretation. Conclusions: Although static and dynamic FC are likely to be a useful tool to detect altered RSN in patients affected by AD and other neuropsychiatric disorders, interpretation of altered dynamic FC in patients require special care. Impact statement We review recent studies of static and dynamic functional connectivity (dFC) in Alzheimer's disease and discuss interpretation of dFC.

Metabolic changes in the plasma of mild Alzheimer's disease patients treated with Hachimijiogan.

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.

Modes of inheritance of two apomixis components, diplospory and parthenogenesis, in Chinese chive (Allium ramosum) revealed by analysis of the segregating population generated by back-crossing between amphimictic and apomictic diploids.

To investigate the mode of inheritance of apomixis in Chinese chive, the degrees of diplospory and parthenogenesis were evaluated in F(1) and BC(1) progenies derived from crosses between amphimictic and apomictic diploids (2n = 16, 2x). The F(1) population was generated by crossing three amphimictic diploids 94Mo13, 94Mo49 and 94Mo50 with an apomictic diploid KaD2 and comprised 110 diploids and 773 triploids. All the diploid F(1) plants examined were completely or highly eusporous and completely syngamic. All the triploid F(1) plants examined were highly diplosporous and highly parthenogenetic. KaD2 could not transmit its high level of apomixis via monoploid pollen grains. The BC(1) population, generated by crossing 94Mo49 with apomictic triploids found in the F(1) offspring, exhibited heteroploidy; it comprised haploid, diploid, triploid, tetraploid and various aneuploid individuals. In this generation, clear segregation was observed between diplospory and parthenogenesis. Analysis of the BC(1) population suggests that diplospory and parthenogenesis are each controlled by single dominant genes, D and P, respectively. However, all the BC(1) plants characterized as parthenogenetic were diplosporous. The absence of phenotypically eusporous parthenogenetic plants can be explained by assuming that the presence of diplospory gene is a prerequisite for the parthenogenesis gene expression in Chinese chive.

Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging.

Background: Alzheimer's disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported. Objective: We aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months. Methods: Seventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy. Results: Responders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change. Conclusion: The negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.

An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.

Direct determination of the chromosomal location of bunching onion and bulb onion markers using bunching onion-shallot monosomic additions and allotriploid-bunching onion single alien deletions.

To determine the chromosomal location of bunching onion (Allium fistulosum L.) simple sequence repeats (SSRs) and bulb onion (A. cepa L.) expressed sequence tags (ESTs), we used a complete set of bunching onion-shallot monosomic addition lines and allotriploid bunching onion single alien deletion lines as testers. Of a total of 2,159 markers (1,198 bunching onion SSRs, 324 bulb onion EST-SSRs and 637 bulb onion EST-derived non-SSRs), chromosomal locations were identified for 406 markers in A. fistulosum and/or A. cepa. Most of the bunching onion SSRs with identified chromosomal locations showed polymorphism in bunching onion (89.5%) as well as bulb onion lines (66.1%). Using these markers, we constructed a bunching onion linkage map (1,261 cM), which consisted of 16 linkage groups with 228 markers, 106 of which were newly located. All linkage groups of this map were assigned to the eight basal Allium chromosomes. In this study, we assigned 513 markers to the eight chromosomes of A. fistulosum and A. cepa. Together with 254 markers previously located on a separate bunching onion map, we have identified chromosomal locations for 766 markers in total. These chromosome-specific markers will be useful for the intensive mapping of desirable genes or QTLs for agricultural traits, and to obtain DNA markers linked to these.

[Spontaneous disappearance of intracranial arteriovenous malformation after living-donor liver transplantation: a case report].

In this report, the authors describe a 35-year-old male whose intracranial arteriovenous malformation (AVM) spontaneously disappeared about 2 years after successful living-donor liver transplantation for alcohol-induced liver cirrhosis. Preoperative screening MRI revealed intracranial arteriovenous malformation (AVM) around the midbrain. Cerebral angiography demonstrated that the AVM was fed by the paramedian mesencephalic arteries and was drained via the vein of Galen. He successfully underwent living-donor liver transplantation, and his postoperative course was uneventful. Follow-up MRI and MRA revealed spontaneous disappearance of the AVM 27 months after surgery. The authors discuss precisely the underlying mechanism of this rare phenomenon, based on thorough literature review.

Preparation to inhibit a response complements response inhibition during performance of a stop-signal task.

Inhibition of inappropriate responses is an essential executive function needed for adaptation to changing environments. In stop-signal tasks, which are often used to investigate response inhibition, subjects make "go" responses while they prepare to stop at a suddenly given "stop" signal. However, the preparatory processes ongoing before response inhibition have rarely been investigated, and it remains unclear how the preparation contributes to response inhibition. In the present study, a stop-signal task was designed so that the extent of the preparation could be estimated using behavioral and neuroimaging measures. Specifically, in addition to the conventional go trials where preparation to stop was required ("uncertain-go" trials), another type of go trial was introduced where a stop-signal was never given and such preparation was unnecessary ("certain-go" trials). An index reflecting the "preparation cost" was then calculated by subtracting the reaction times in the certain-go trials from those in the uncertain-go trials. It was revealed that the stop signal reaction time, a common index used to evaluate the efficiency of response inhibition, decreased as the preparation cost increased, indicating greater preparation supports more efficient inhibition. In addition, imaging data showed that response inhibition recruited frontoparietal regions (the contrast "stop vs uncertain-go") and that preparation recruited most of the inhibition-related frontoparietal regions (the contrast "uncertain-go vs certain-go"). It was also revealed that the inhibition-related activity declined as the preparation cost increased. These behavioral and imaging results suggest preparation makes a complementary contribution to response inhibition during performance of a stop-signal task.

Formation of long-term memory representation in human temporal cortex related to pictorial paired associates.

It is widely held that long-term memory gradually develops in the temporal neocortex after initial memory encoding into the hippocampus. However, little is known as to whether and where long-term memory can be newly created in the human temporal neocortex. In this functional magnetic resonance imaging study, we detected brain activity in the temporal neocortex that was developed approximately 8 weeks after study of unfamiliar pictorial paired associates. Two sets of paired Fourier figures were studied, one approximately 8 weeks before test and the other immediately before test, keeping the correct performance during the tests balanced across the two sets of stimuli. Significant signal increase was observed in the right hippocampus during retrieval of newly studied pairs relative to initially studied pairs. In contrast, significant signal increase was observed in the anterior temporal cortex during retrieval of initially studied pairs relative to newly studied pairs. The greater activity during retrieval of older memory developed in the temporal neocortex provides direct evidence of formation of temporal neocortical representation for stable long-term memory.

Functional dissociation in right inferior frontal cortex during performance of go/no-go task.

The contribution of the right inferior frontal cortex to response inhibition has been demonstrated by previous studies of neuropsychology, electrophysiology, and neuroimaging. The inferior frontal cortex is also known to be activated during processing of infrequent stimuli such as stimulus-driven attention. Response inhibition has most often been investigated using the go/no-go task, and the no-go trials are usually given infrequently to enhance prepotent response tendency. Thus, it has not been clarified whether the inferior frontal activation during the go/no-go task is associated with response inhibition or processing of infrequent stimuli. In the present functional magnetic resonance imaging study, we employed not only frequent-go trials but also infrequent-go trials that were presented as infrequently as the no-go trials. The imaging results demonstrated that the posterior inferior frontal gyrus (pIFG) was activated during response inhibition as revealed by the no-go vs. infrequent-go trials, whereas the inferior frontal junction (IFJ) region was activated primarily during processing of infrequent stimuli as revealed by the infrequent-go versus frequent-go trials. These results indicate that the pIFG and IFJ within the inferior frontal cortex are spatially close but are associated with different cognitive control processes in the go/no-go paradigm.

The efficacy and safety of hachimijiogan for mild Alzheimer disease in an exploratory, open standard treatment controlled, randomized allocation, multicenter trial: A study protocol.

BACKGROUND: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. METHODS/DESIGN: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD.Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. DISCUSSION: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. TRIAL REGISTRATION: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).

Disconnection of the right superior parietal lobule from the precuneus is associated with memory impairment in oldest-old Alzheimer's disease patients.

There is a wide range of onset age in Alzheimer's disease (AD). Emerging evidence indicates variation of AD manifestations in oldest-old AD (OOAD); however, the pattern of cognitive dysfunctions remains unclear. We aimed to reveal cognitive performance characteristics and changes in brain functional connectivity in OOAD patients by a resting-state fMRI (rs-fMRI) study. We enrolled AD patients who had been referred to Kyushu University Hospital (KUH) or Sanno Hospital, and classified them into middle-old AD (MOAD) (65-79 years old) and OOAD (≥80 years old) according to the age of onset. Our subjects consisted of 19 OOAD, 17 MOAD, and 8 normal subjects. Cognitive performance was evaluated using Mini Mental State Examination-Japanese (MMSE-J) and Clinical Dementia Rating (CDR). rs-fMRI scanning and independent component analysis (ICA) were performed on Sanno Hospital patients and MOAD vs. OOAD patients were compared. The resulting significant regions were used as seeds for ROI-to-ROI analysis of the KUH dataset. Collectively, MMSE-J delayed recall sub-scores were significantly lower in OOAD patients compared with MOAD patients. ICA of the Sanno Hospital data indicated significant connectivity decrease in the default mode network (DMN) in the OOAD group compared with the MOAD group in the right superior parietal lobule (SPL). ROI-to-ROI analysis of the KUH dataset indicated significant disconnection in the OOAD group of the right SPL from the precuneus (p < 0.01). The functional connectivity from the right SPL to the precuneus was positively correlated with the MMSE-J delayed recall sub-score (p = 0.03) and negatively correlated with the CDR memory sub-scale (p = 0.04). These findings indicate that disconnection between the right SPL and the precuneus may contribute to worse memory capability in OOAD compared with MOAD.

Optic, trigeminal, and facial neuropathy related to anti-neurofascin 155 antibody.

OBJECTIVE: To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 anti-neurofascin 155 antibody-positive (NF155+ ) chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirteen IgG4 NF155+ CIDP patients with mean onset age of 34 years (11 men) were subjected to neurological examination, blink reflex, and visual-evoked potential (VEP) testing, and axial and/or coronal T2-weighted head magnetic resonance imaging (MRI). RESULTS: Among 13 patients, facial sensory impairment, facial weakness, and apparent visual impairment were observed in three (23.1%), two (15.4%), and two (15.4%) patients, respectively. All 12 patients tested had blink reflex abnormalities: absent and/or delayed R1 in 11 (91.7%), and absent and/or delayed R2 in 10 (83.3%). R1 latencies had strong positive correlations with serum anti-NF155 antibody levels (r = 0.9, P ≤ 0.0001 on both sides) and distal and F wave latencies of the median and ulnar nerves. Absent and/or prolonged VEPs were observed in 10/13 (76.9%) patients and 17/26 (65.4%) eyes. On MRI, hypertrophy, and high signal intensity of trigeminal nerves were detected in 9/13 (69.2%) and 10/13 (76.9%) patients, respectively, whereas optic nerves were normal in all patients. The intra-orbital trigeminal nerve width on coronal sections showed a significant positive correlation with disease duration. INTERPRETATION: Subclinical demyelination frequently occurs in the optic, trigeminal, and facial nerves in IgG4 NF155+ CIDP, suggesting that both central and peripheral myelin structures of the cranial nerves are involved in this condition, whereas nerve hypertrophy only develops in myelinated peripheral nerve fibers.

Sub-centimeter scale functional organization in human inferior frontal gyrus.

Functional areas in sensory/motor cortices are usually organized, on a finer scale, in a seamless manner along related functional units that represent, for example, certain visual fields to analyze and certain body parts to control. However, fine-scale functional organization in the prefrontal cortex has rarely been reported. In the present functional magnetic resonance imaging study, we show an example of sub-centimeter scale functional organization in the posterior part of the inferior frontal gyrus (IFG) in the right hemisphere. The spatial relationship was examined in the same subjects with regard to the activations associated with response inhibition and negative feedback processing, which are known to activate similar right IFG regions. We found that these activations were segregated, the activation during response inhibition being more caudal than that during feedback processing, and that the distance between the two activations was only 8.7 mm. Examination of the two-dimensional surface mapping of individual subjects confirmed that the two activations were located in adjacent but different regions. These results provide a specific example of a pair of functionally characterized regions that are located in the close vicinity within the right IFG.

A critical component that activates the left inferior prefrontal cortex during interference resolution.

Previous studies of proactive interference (PI) have revealed the involvement of the left inferior frontal gyrus (IFG) in resolution of PI during working memory/item recognition. PI resolution is thought to require: (1) inhibition of inappropriate attribution of familiarity to the probe and resultant inappropriate response tendencies; and (2) inhibition of PI per se regardless of the appropriateness of the attribution of familiarity. It is not clear, however, whether the IFG supports inhibition of inappropriate response tendencies or inhibition of PI per se. In the present functional magnetic resonance imaging study, we dissociate these possibilities using a recency judgment paradigm. Recency judgments, judgments of the relative temporal order of two studied items, provided an opportunity of examining three types of trials that differed in the way PI influenced the current trials: the trials where PI from previous trials was congruent with the current trials (C-PI trials); the trials where PI was incongruent with the current trials (I-PI trials); and the trials where no PI influenced the current trials (N-PI trials). Relative to the N-PI trials, the I-PI trials elicited the significant left IFG activation associated with PI resolution, consistent with previous studies using working memory/item recognition. We found that the IFG activation was related not to inhibition of inappropriate response tendencies (I-PI vs. C-PI), but to inhibition of PI per se (C-PI vs. N-PI). These results indicate that the left IFG plays its control role regardless of whether or not PI is congruent with correct performance of current trials.

Functional connectivity change between posterior cingulate cortex and ventral attention network relates to the impairment of orientation for time in Alzheimer's disease patients.

Alzheimer's disease (AD) patients exhibit various cognitive dysfunctions, including impairment of orientation for time (OT). The brain regions underlying OT impairment remain to be elucidated. A previous single-photon emission computed tomography study has indicated hypoperfusion of the posterior cingulate cortex (PCC) in relation to deterioration of OT. In this study, we investigated whole brain functional connectivity changes of PCC using resting-state functional magnetic resonance imaging. Voxel-based functional connectivity with PCC was analyzed in OT-poor or OT-good AD patients, classified according to the mean OT scores of the Mini-Mental State Examination subscale. The connectivities of dorsal frontal lobe, and lateral parietal and lateral temporal lobes with PCC in the right hemisphere were reduced in the OT-poor AD group compared with the OT-good AD group. A subtraction connectivity map of OT score differences (OT-good minus OT-poor) revealed the right middle temporal gyrus near the temporo-parietal junction as a significantly connected region with PCC. These results suggest that the right posterior part of the middle temporal gyrus may play an important role in OT in conjunction with PCC, and that disconnection between PCC and the right ventral attention network may cause OT disturbance in AD patients.