State-unspecific patterns of whole-brain functional connectivity from resting and multiple task states predict stable individual traits.

An increasing number of functional magnetic resonance imaging (fMRI) studies have revealed potential neural substrates of individual differences in diverse types of brain function and dysfunction. Although most previous studies have inherently focused on state-specific characterizations of brain networks and their functions, several recent studies reported on the potential state-unspecific nature of functional brain networks, such as global similarities across different experimental conditions or states, including both task and resting states. However, no previous studies have carried out direct, systematic characterizations of state-unspecific brain networks, or their functional implications. Here, we quantitatively identified several modes of state-unspecific individual variations in whole-brain functional connectivity patterns, called "Common Neural Modes" (CNMs), from a large-scale fMRI database including eight task/resting states. Furthermore, we tested how CNMs accounted for variability in individual cognitive measures. The results revealed that three CNMs were robustly extracted under various dimensions of features used. Each of these CNMs was preferentially correlated with different aspects of representative cognitive measures, reflecting stable individual traits. Importantly, the association between CNMs and cognitive measures emerged from brain connectivity data alone ("unsupervised"), whereas previous related studies have explicitly used both connectivity and cognitive measures to build their prediction models ("supervised"). The three CNMs were also able to predict several life outcomes, including income and life satisfaction, and achieved the highest level of performance when combined with a conventional cognitive measure. Our findings highlight the importance of state-unspecific brain networks in characterizing fundamental individual variation.

A common brain network among state, trait, and pathological anxiety from whole-brain functional connectivity.

Anxiety is one of the most common mental states of humans. Although it drives us to avoid frightening situations and to achieve our goals, it may also impose significant suffering and burden if it becomes extreme. Because we experience anxiety in a variety of forms, previous studies investigated neural substrates of anxiety in a variety of ways. These studies revealed that individuals with high state, trait, or pathological anxiety showed altered neural substrates. However, no studies have directly investigated whether the different dimensions of anxiety share a common neural substrate, despite its theoretical and practical importance. Here, we investigated a brain network of anxiety shared by different dimensions of anxiety in a unified analytical framework using functional magnetic resonance imaging (fMRI). We analyzed different datasets in a single scale, which was defined by an anxiety-related brain network derived from whole brain. We first conducted the anxiety provocation task with healthy participants who tended to feel anxiety related to obsessive-compulsive disorder (OCD) in their daily life. We found a common state anxiety brain network across participants (1585 trials obtained from 10 participants). Then, using the resting-state fMRI in combination with the participants' behavioral trait anxiety scale scores (879 participants from the Human Connectome Project), we demonstrated that trait anxiety shared the same brain network as state anxiety. Furthermore, the brain network between common to state and trait anxiety could detect patients with OCD, which is characterized by pathological anxiety-driven behaviors (174 participants from multi-site datasets). Our findings provide direct evidence that different dimensions of anxiety have a substantial biological inter-relationship. Our results also provide a biologically defined dimension of anxiety, which may promote further investigation of various human characteristics, including psychiatric disorders, from the perspective of anxiety.

[The efficacy of neoadjuvant chemotherapy with S-1/CDDP (SP) to the patients with large type 3 and type 4 gastric cancer].

Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

Narrow-band imaging on screening of esophageal lesions using an ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Ultrathin transnasal endoscopy, used extensively in Japan, is considered to have inferior image quality and suction performance, and questionable diagnostic performance. So the aim of the present study was to compare the diagnostic performance of white light (WL) examination and non-magnified narrow-band imaging (NBI) examination in screening for esophageal disorders with ultrathin transnasal endoscopy. METHODS: A prospective case study of 105 consecutive patients screened for upper gastrointestinal disorders at a single clinic in Tokyo Medical University Hospital. All subjects were diagnosed using WL, NBI and Lugol-staining examinations. Areas ≥ 5 mm clearly not a Lugol-staining lesion were defined as esophageal disorders and the rates of detection of the two examination methods (WL vs NBI) were compared. RESULTS: For WL examination, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy (concordance rate) for esophageal disorders were 19.6%, 98.1%, 90.9%, 55.4%, and 59.2%, respectively, versus 60.8% 96.2%, 93.9%, 71.4%, and 78.6% for NBI. CONCLUSION: A useful level of diagnostic performance for esophageal disorders can be achieved with non-magnified narrow-band NBI ultrathin transnasal endoscopy.

[A case that showed an improved quality of life for rectal gastrointestinal stromal tumor patient treated with cytoreductive surgery].

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

Relationship between nuclei-specific amygdala connectivity and mental health dimensions in humans.

There has been increasing interest in using neuroimaging measures to predict psychiatric disorders. However, predictions usually rely on large brain networks and large disorder heterogeneity. Thus, they lack both anatomical and behavioural specificity, preventing the advancement of targeted interventions. Here we address both challenges. First, using resting-state functional magnetic resonance imaging, we parcellated the amygdala, a region implicated in mood disorders, into seven nuclei. Next, a questionnaire factor analysis provided subclinical mental health dimensions frequently altered in anxious-depressive individuals, such as negative emotions and sleep problems. Finally, for each behavioural dimension, we identified the most predictive resting-state functional connectivity between individual amygdala nuclei and highly specific regions of interest, such as the dorsal raphe nucleus in the brainstem or medial frontal cortical regions. Connectivity in circumscribed amygdala networks predicted behaviours in an independent dataset. Our results reveal specific relations between mental health dimensions and connectivity in precise subcortical networks.

[A case of liver metastases from gastric cancer treated with stereotactic body radiation therapy].

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

Adapting non-invasive human recordings along multiple task-axes shows unfolding of spontaneous and over-trained choice.

Choices rely on a transformation of sensory inputs into motor responses. Using invasive single neuron recordings, the evolution of a choice process has been tracked by projecting population neural responses into state spaces. Here, we develop an approach that allows us to recover similar trajectories on a millisecond timescale in non-invasive human recordings. We selectively suppress activity related to three task-axes, relevant and irrelevant sensory inputs and response direction, in magnetoencephalography data acquired during context-dependent choices. Recordings from premotor cortex show a progression from processing sensory input to processing the response. In contrast to previous macaque recordings, information related to choice-irrelevant features is represented more weakly than choice-relevant sensory information. To test whether this mechanistic difference between species is caused by extensive over-training common in non-human primate studies, we trained humans on >20,000 trials of the task. Choice-irrelevant features were still weaker than relevant features in premotor cortex after over-training.

Intergenerational transmission of the patterns of functional and structural brain networks.

There is clear evidence of intergenerational transmission of life values, cognitive traits, psychiatric disorders, and even aspects of daily decision making. To investigate biological substrates of this phenomenon, the brain has received increasing attention as a measurable biomarker and potential target for intervention. However, no previous study has quantitatively and comprehensively investigated the effects of intergenerational transmission on functional and structural brain networks. Here, by employing an unusually large cohort dataset (N = 84 parent-child dyads; 45 sons, 39 daughters, 81 mothers, and 3 fathers), we show that patterns of functional and structural brain networks are preserved over a generation. We also demonstrate that several demographic factors and behavioral/physiological phenotypes have a relationship with brain similarity. Collectively, our results provide a comprehensive picture of neurobiological substrates of intergenerational transmission and demonstrate the usability of our dataset for investigating the neurobiological substrates of intergenerational transmission.

Helicobacter pylori infection and reflux esophagitis in young and middle-aged Japanese subjects.

BACKGROUND AND AIMS: Helicobacter pylori infection rates are reported to be high in people over the age of 40 years, but are decreasing in younger age groups. A negative correlation has been reported between H. pylori infection and reflux esophagitis (RE). METHODS: The subjects were 418 patients who underwent esophagogastroduodenoscopy and measurement of serum immunoglobulin G H. pylori antibodies examined as part of their routine health checks. Their mean age was 39.2 +/- 8.3 years (range 22-58). We analyzed the RE findings (Los Angeles classification: A, B, C, D). RESULTS: The total H. pylori infection rate was 33.7% (141/418). By age group, infection rates were 15.7% in the 20-29 years group, 28.0% in the 30-39 group, 34.3% in the 40-49 group and 69.1% in the 50-59 group. The proportion of H. pylori-negative subjects with RE was 23.5% (20-29, 22.9%; 30-39, 31.7%; 40-49, 32.4%; 50-59, 41.7%), significantly higher than that (12.1%) in H. pylori-positive subjects (20-29, 0%; 30-39, 16.7%; 40-49, 12.2%; 50-59, 10.5%). The severity of RE increased with advancing age in H. pylori-positive subjects, but not in H. pylori-negative subjects. CONCLUSION: In this study, higher rates of RE were seen in H. pylori-negative subjects. It may be, however, that the presence of H. pylori infection influences the progression of RE.

[A long-term survival case of hepatic metastases after curative gastrectomy by combined therapies].

A 74-year-old female was performed distal gastrectomy (f-T3N0H0P0CY0M0, Stage II) for gastric cancer in 2003. After 14 months, CT scan showed a metastasis in S7 segment of the liver. We performed chemotherapies until seventh-line and radio-frequency ablation (RFA). It finally got a long-term survival of 36 months postoperatively. RFA may be one of the useful therapies of liver metastasis from gastric cancer.

Tailored eradication therapy based on fecal Helicobacter pylori clarithromycin sensitivities.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) eradication rates using the PPI/AC regimen (proton pump inhibitor + amoxicillin + clarithromycin) are declining. We trialed tailoring eradication regimens according to clarithromycin (CAM) susceptibility. METHODS: The subjects were 70 H. pylori positive adults. They were randomly allocated to a tailored group and a control group. In the tailored group, subjects with CAM-sensitive strains were given PPI/AC eradication therapy, and those with CAM-resistant strains were given PPI/AM (metronidazole instead of clarithromycin) therapy. The control group were all given PPI/AC therapy. CAM sensitivity was measured by collecting fecal specimens, and extracting the DNA. The 23S rRNA domain, associated with CAM susceptibility in H. pylori, was amplified using a nested polymerase chain reaction (PCR), and DNA sequencing was used to detect point mutations at A2143G and A2144G. RESULTS: Eradication rates were 94.3% in the tailored group and 71.4% in the control group. In particular, the eradication rate was 100% for CAM-resistant strains in the tailored group. CONCLUSIONS: In Japan, where CAM-resistant H. pylori strains are expected to continue to increase, tailored eradication therapy according to CAM sensitivity will be of benefit.

Impact of transnasal ultrathin esophagogastroduodenoscopy (UT-EGD) in the evaluation of esophageal peristaltic function.

BACKGROUND: We used transnasal ultrathin esophagogastroduodenoscopy (UT-EGD) to simultaneously perform realtime esophageal manometry and observe esophageal peristalsis. METHODS: The subjects were 22 healthy volunteers and 10 patients with proton-pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). We induced the primary peristaltic wave associated with swallowing and observed it endoscopically in the lower esophagus, at the same time measuring the intraesophageal pressure using a manometry catheter. RESULTS: The mean primary peristaltic amplitude associated with swallowing was 65.6+/-47.4 mmHg in the volunteer group, and 28.0+/-25.6 mmHg in the GERD group. Although peristalsis was observed endoscopically in the GERD group, in some cases incomplete peristalsis left a small but definite lumen and in these subjects, the primary peristaltic wave was almost flat. CONCLUSIONS: The use of an ultrathin transnasal endoscope makes possible simultaneous manometry and endoscopic observation of the esophagus. This combination should prove useful in the evaluation of esophageal peristaltic function, such as in the diagnosing of GERD.

A study of the relationship between Helicobacter pylori microbial susceptibility, 13C-urea breath test values.

BACKGROUND/AIMS: Diagnostic methods for Helicobacter pylori (H. pylori) infection can be divided into invasive endoscopic methods and non-invasive methods. A typical and widely used non-invasive method is the 13C urea breath test (UBT). In this study, the possibility of a correlation between pre-treatment UBT values with H. pylori antimicrobial resistance is investigated. METHODOLOGY: The subjects were 119 consecutive patients who attended this hospital for H. pylori testing. Average age was 47.5 +/- 13.2 years, with a male:female ratio of 2.05:1. The diagnosis was gastric ulcer in 43 subjects, duodenal ulcer in 27, gastroduodenal ulcer in 21 and chronic gastritis in 28. Subjects underwent UBT as well as upper gastrointestinal endoscopy (UGITE). The diagnosis of H. pylori infection was examined by the results of culture, histological examination and the rapid urease test (RUT). The mean inhibitory concentration (MIC) was determined for each antimicrobial agent in the bacterial isolates that could be cultured. RESULTS: In this study, the sensitivity and specificity were excellent at 97.0% and 100% with a cut-off point of 3.5 per thousand for UBT respectively. Clarithromycin resistance was more common in the group with high UBT values. No correlation at all was seen between UBT values and metronidazole, sparafloxacin, cefaclor and amoxicillin susceptibility. CONCLUSIONS: It is possible that UBT values also tend to be higher in cases of CAM resistance.

[A case report of long-term survival of advanced gastric cancer (P1CY1) after gastrectomy].

A-57-year-old male was performed a total gastrectomy (f-T3N2H0P1CY1M0, Stage IV) for gastric cancer in 2004. We kept performing chemotherapies until the seventh-line, and the patient at last had a long-term survival of 46 months after surgery. If we recognized a tumor that had a tendency to be progressive, the long-term survival may be obtained by changing a regimen as early as possible.

[A case of stenosis of the reconstructed jejunum due to recurrent cancer after total gastrectomy in which stent-in-stent placement was effective].

OBJECTIVES: We report one case of stenosis of the reconstructed jejunum due to recurrent cancer after total gastrectomy in which stenting was effective and good QOL was achieved. CASE: The patient was a 70-year-old woman. In July 2000, the patient underwent total gastrectomy.Roux-en Y reconstruction with a diagnosis of gastric cancer. The pathological diagnosis was U-Post, Type 3, por 1, T3, N1, H0, P0, CY0, M0, and Stage IIIA. From 9 months after the operation, aphagia occurred and stenosis of the reconstructed jejunum was noted. Based on a biopsy of the stenosis, a diagnosis of post-operative recurrent gastric cancer was made. Although the patient received two cycles of low-dose FP therapy, complete response was not obtained, and the patient stayed at home under the IVH control for about 4 months. In June 2001, the patient was hospitalized for a stent placement due to the patient's request. METHOD: After a guide wire was endoscopically inserted and a good passage on the anal side of the stenosis was confirmed, a stent was placed. Self Expandable Metallic Stent (SEMS) was used. CLINICAL COURSE: Following the stent placement, the patient was able to ingest orally, but 6.5 months later, stenotic symptoms developed and another stent was deployed (stent in stent). CONCLUSION: Stenting is relatively simple and less invasive, which is useful for the improvement of QOL and in recurrent cases as well.

Usefulness of serum protein profiling for prediction of preoperative chemoradiosensitivity of esophageal cancer.

We examined whether serum protein profiling is a reliable index for prediction of therapeutic efficacy of preoperative chemoradiotherapy (PCRT) in advanced esophageal cancer compared with evaluation of the efficacy of conventional clinical examination. We entered 42 patients who received PCRT and surgery between 1998 and 2002 into this study. Serum protein profiling was performed using the preoperative serum of the patient to select the marker set that enabled the efficacy of PCRT to be evaluated accurately. The efficacy of PCRT was predicted with the marker set, and the sensitivity, specificity and accuracy of the method were calculated based on evaluation of the efficacy by pathological examination. Similarly, therapeutic efficacy was also predicted based on evaluation of the efficacy of conventional clinical examination, and the results were compared with those of prediction by serum protein profiling. The correlation between each predictive examination and outcome was evaluated. The sensitivity, specificity and accuracy of prediction of therapeutic efficacy of PCRT by serum protein profiling were 90.9, 100 and 93.3%, respectively. In clinical examination, prediction of the efficacy of PCRT by three methods was as follows: by esophagography, sensitivity 76.0%, specificity 17.6%, accuracy 52.4%; by endoscopy, sensitivity 80.0%, specificity 11.8%, accuracy 52.4%; by computed tomography, sensitivity 60.0%, specificity 47.1%, accuracy 54.8%, respectively. These results demonstrated the superiority of serum protein profiling in predicting the therapeutic efficacy of PCRT compared with conventional clinical examination. Moreover, serum protein profiling was the only significant prognostic factor as regards the correlation with outcome by multivariate analysis.

[Long survival and effective treatment of unresectable gastric cancer by TS-1 based chemotherapy with a sequential combination].

We report a case of peritoneal cancer dissemination and cytological appearance of cancer cells with Type 4 gastric cancer. Treatment with unichemotherapy and combination chemotherapy with TS-1 proved successful. The patient was a 58-year-old female,who complained of abdominal pain. She was diagnosed as unresectable Type 4 gastric cancer, T 3 NxH 0 P 1 CY 1 M 0, Stage IV (cytology: Class V). Thirteen days after surgery, chemotherapy with TS-1 (80 mg/body/day, 4 weeks) at 2-week intervals in 1 course was performed. However, due to side effects with marrow restraint of grade 1, we changed to the following chemotherapy regimen: TS-1 (80 mg/body/day, 2 weeks) at 4-week intervals as 1 course (23 courses in total). After 16 courses, a partial response (PR) was noted. As additional therapy to recover tumor marker (CA19-9) after 21 courses, combination chemotherapy with TS-1 (80 mg/body/day, 2 weeks) and CDDP (25 mg/body/day, day 1, 8, 15 drip infusion) was performed as one course. This chemotherapy was then performed in 3 courses and tumor markers did not deteriorate, so we changed docetaxel (DOC) (50 mg/body/day(day 1)) to CDDP, and tumor markers returned to the normal value. No recurrence and no side effects appeared (hematological or non-hematological) during this combination chemotherapy.

[A long-term survival case of metachronous liver metastasis from gastric cancer].

A 62-year-old man was admitted for gastric cancer. He was performed a distal gastrectomy with Billroth I reconstruction in August 1999. Then he had remnant gastric cancer and metachronous liver cancer in November 2002. He was performed a total gastrectomy and partial hepatic resection. The histological findings of remnant stomach and liver cancer showed a same pattern of the primary gastric cancer. Another metachronous liver cancer appeared in March 2006. He was treated with chemotherapy using S-1 (day 1-21) and CDDP 20 mg/m2 (day 1, 8 and 15) q5w. The size of liver metastasis was kept the same for 16 months.

A Neural Marker of Obsessive-Compulsive Disorder from Whole-Brain Functional Connectivity.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.