Echoes from Intrinsic Connectivity Networks in the Subcortex.

Decades of research have greatly improved our understanding of intrinsic human brain organization in terms of functional networks and the transmodal hubs within the cortex at which they converge. However, substrates of multinetwork integration in the human subcortex are relatively uncharted. Here, we leveraged recent advances in subcortical atlasing and ultra-high field (7 T) imaging optimized for the subcortex to investigate the functional architecture of 14 individual structures in healthy adult males and females with a fully data-driven approach. We revealed that spontaneous neural activity in subcortical regions can be decomposed into multiple independent subsignals that correlate with, or "echo," the activity in functional networks across the cortex. Distinct subregions of the thalamus, striatum, claustrum, and hippocampus showed a varied pattern of echoes from attention, control, visual, somatomotor, and default mode networks, demonstrating evidence for a heterogeneous organization supportive of functional integration. Multiple network activity furthermore converged within the globus pallidus externa, substantia nigra, and ventral tegmental area but was specific to one subregion, while the amygdala and pedunculopontine nucleus preferentially affiliated with a single network, showing a more homogeneous topography. Subregional connectivity of the globus pallidus interna, subthalamic nucleus, red nucleus, periaqueductal gray, and locus coeruleus did not resemble patterns of cortical network activity. Together, these finding describe potential mechanisms through which the subcortex participates in integrated and segregated information processing and shapes the spontaneous cognitive dynamics during rest.SIGNIFICANCE STATEMENT Despite the impact of subcortical dysfunction on brain health and cognition, large-scale functional mapping of subcortical structures severely lags behind that of the cortex. Recent developments in subcortical atlasing and imaging at ultra-high field provide new avenues for studying the intricate functional architecture of the human subcortex. With a fully data-driven analysis, we reveal subregional connectivity profiles of a large set of noncortical structures, including those rarely studied in fMRI research. The results have implications for understanding how the functional organization of the subcortex facilitates integrative processing through cross-network information convergence, paving the way for future work aimed at improving our knowledge of subcortical contributions to intrinsic brain dynamics and spontaneous cognition.

Charting human subcortical maturation across the adult lifespan with in vivo 7 T MRI.

The human subcortex comprises hundreds of unique structures. Subcortical functioning is crucial for behavior, and disrupted function is observed in common neurodegenerative diseases. Despite their importance, human subcortical structures continue to be difficult to study in vivo. Here we provide a detailed account of 17 prominent subcortical structures and ventricles, describing their approximate iron and myelin contents, morphometry, and their age-related changes across the normal adult lifespan. The results provide compelling insights into the heterogeneity and intricate age-related alterations of these structures. They also show that the locations of many structures shift across the lifespan, which is of direct relevance for the use of standard magnetic resonance imaging atlases. The results further our understanding of subcortical morphometry and neuroimaging properties, and of normal aging processes which ultimately can improve our understanding of neurodegeneration.

Joint Modelling of Latent Cognitive Mechanisms Shared Across Decision-Making Domains.

Decision-making behavior is often understood using the framework of evidence accumulation models (EAMs). Nowadays, EAMs are applied to various domains of decision-making with the underlying assumption that the latent cognitive constructs proposed by EAMs are consistent across these domains. In this study, we investigate both the extent to which the parameters of EAMs are related between four different decision-making domains and across different time points. To that end, we make use of the novel joint modelling approach, that explicitly includes relationships between parameters, such as covariances or underlying factors, in one combined joint model. Consequently, this joint model also accounts for measurement error and uncertainty within the estimation of these relations. We found that EAM parameters were consistent between time points on three of the four decision-making tasks. For our between-task analysis, we constructed a joint model with a factor analysis on the parameters of the different tasks. Our two-factor joint model indicated that information processing ability was related between the different decision-making domains. However, other cognitive constructs such as the degree of response caution and urgency were only comparable on some domains.

A high-resolution 7 Tesla resting-state fMRI dataset optimized for studying the subcortex.

To achieve a comprehensive understanding of spontaneous brain dynamics in humans, in vivo acquisition of intrinsic activity across both cortical and subcortical regions is necessary. Here we present advanced whole-brain, resting-state functional magnetic resonance imaging (rs-fMRI) data acquired at 7 Tesla with 1.5 mm isotropic voxel resolution. Functional images were obtained from 56 healthy adults (33 females, ages 19-39 years) in two runs of 15 min eyes-open wakeful rest. The high spatial resolution and short echo times of the multiband echo-planar imaging (EPI) protocol optimizes blood oxygen level-dependent (BOLD)-sensitivity for the subcortex while concurrent respiratory and cardiac measures enable retrospective correction of physiological noise, resulting in data that is highly suitable for researchers interested in subcortical BOLD signal. Functional timeseries were coregistered to high-resolution T1-weighted structural data (0.75 mm isotropic voxels) acquired during the same scanning session. To accommodate data reutilization, functional and structural images were formatted to the Brain Imaging Data Structure (BIDS) and preprocessed with fMRIPrep.

A high-resolution multi-shell 3T diffusion magnetic resonance imaging dataset as part of the Amsterdam Ultra-high field adult lifespan database (AHEAD).

In order to further our understanding of brain function and the underlying networks, more advanced diffusion weighted magnetic resonance imaging (DWI MRI) data are essential. Here we present freely available high-resolution multi-shell multi-directional 3 Tesla (T) DWI MRI data as part of the 'Amsterdam Ultra-high field adult lifespan database' (AHEAD). The 3T DWI AHEAD dataset include 1.28mm isotropic whole brain DWI data of 49 healthy adult participants between 18 and 90 years old. The acquired data include DWIs at three non-zero b-values (48 directions, b-value 700 s/mm2; 56 directions, b-value 1000 s/mm2; 64 directions, b-value 1600 s/mm2) including a total of twelve volumes with a b-value of 0 s/mm2 (b0 volumes). In addition, eight b0 volumes with a reversed phase encoding direction were acquired to correct for distortions. To facilitate future use, the DWI data have been denoised, corrected for eddy currents, susceptibility-induced off-resonance field distortions, bias fields, and are skull stripped.

The effect of cysteamine, cystamine, and the structurally related compounds taurine, N-acetyl-cysteine, and D-penicillamine on plasma prolactin levels in normal and estrogen-primed hyperprolactinemic rats.

Studies were undertaken to evaluate the effects of cysteamine (CSH), cystamine (CS-S), N-acetyl-cysteine, D-penicillamine, and a major metabolite of CSh, taurine, on plasma PRL levels in normal and estrogen-primed hyperprolactinemic rats. Both CSH and CS-S caused a marked decrease in plasma PRL concentration in hyperprolactinemic rats. The effects of CSH and CS-S lasted for at least 6 h but returned toward pretreatment levels 24 h later. In normal rats a fall in basal plasma PRL concentration was not readily observed but after stimulation with TRH or metaclopramide, PRL secretion elicited by these stimuli was markedly inhibited by CSH and CS-S. The response to TRH or MCP 24 h after treatment with CSH was variable with CS-S appearing to cause an unexpected increase in PRL release in response to TRH or metaclopramide. The structurally related compounds, taurine, N-acetyl-cysteine, and D-penicillamine did not cause any reduction of plasma PRL levels in hyperprolactinemic rats. This may be due, in the case of taurine, to a loss of the free sulfydryl group, in the case of N-acetyl-cysteine, a change in basicity because of a carboxyl group and derivatization of the amino group and D-penicillamine, again a change in basicity due to a free carboxyl group as well as an altered structural relationship between the free amino and sulfydryl groups. These studies indicate that CSH and CS-S by possible reduction to CSH cause a reversible depletion in plasma PRL in normal and hyperprolactinemic rats. Because both substances inhibit different receptor-mediated stimuli, their mechanism of action is likely to be mediated at a common locus involved with the synthesis and release of PRL.

Laparoscopic Roux-en-Y gastric bypass: a totally intra-abdominal approach--technique and preliminary report.

BACKGROUND: Previous descriptions of a laparoscopic Roux-en-Y gastric bypass, using a circular stapler to perform the gastrojejunal anastomosis, have employed the esophagus as a conduit to introduce the anvil of the stapling device into the stomach. The authors believe that the risk of injury to the esophagus, as well as the difficulty in maneuvering the anvil from the pharynx to the proximal part of the stomach, make this technique less than optimal. In other descriptions (in a porcine model) the anvil has been guided into position through a distal gastrotomy by attaching it to a Prolene suture on a straight needle and directing the needle toward a chosen site. Although the authors prefer this method because it avoids potential esophageal injury, they sought a technique that would be even more precise in anvil placement and would avoid pushing a needle across gastric mucosa. METHODS: The authors have developed a method that is totally intra-abdominal and does not risk injury to the esophagus. The circular stapler is still used, thus giving a consistent, small opening through the gastrojejunal anastomosis. RESULTS: Over a 1-year period, 49 (of 50) patients underwent laparoscopic Roux-en-Y gastric bypass with the described method. The average body mass index dropped from 42.63 to 34.12 over the first postoperative 3 months, with an average loss in excess body weight of 38.5%. The length of hospitalization following the procedure averaged 3.8 days, and the time to return to work (where applicable) was 11.9 days. CONCLUSION: This totally intra-abdominal laparoscopic technique is feasible and advantageous.

Autoantibodies to soluble cellular antigens in unexplained recurrent abortion and infertility.

In 36 women with unexplained primary recurrent abortion, 13 with secondary unexpained recurrent abortion, 25 with primary unexplained infertility, 7 with secondary unexplained infertility and two groups of control women, autoantibodies to soluble cellular antigens were measured by Western blotting to a disaggregated HeLa cell antigen preparation, by counter immunoelectrophoresis and by indirect immunofluorescence. Using Western blotting the women with primary infertility and those with secondary recurrent abortion had a significantly higher prevalence of autoantibodies (P less than 0.01 in each case). This was not shown using the other methods. It is possible that these antibodies could be causally related to the pathology of the conditions studied.

Postconceptional age of surviving preterm low-birth-weight infants at hospital discharge.

BACKGROUND: Prediction of the duration of hospital stay of preterm, low-birth-weight infants currently requires inconvenient referral to published tables. OBJECTIVE: To determine whether postconceptional age (gestational age plus chronologic age) could serve as a useful clinical marker for the more convenient prediction of individual durations of hospital stay. DESIGN: Case series. SETTING: Regional military teaching medical center with level III obstetric and neonatal services. PATIENTS: Nine hundred sixty surviving preterm, low-birth-weight infants in the neonatal intensive care unit. MAIN OUTCOME MEASURE: The strength of the relationship of birth weight to postconceptional age at the time of discharge was tested by analysis of variance. RESULTS: Postconceptional age at the time of hospital discharge varied in a highly predictable manner with birth weight (P<.001). The mean and variance were greatest for infants with very low birth weights and decreased with increasing birth weight. Postconceptional age at the time of discharge reached a minimum of 36.0 +/- 1.4 weeks (mean +/- SD) for infants with birth weights of 1750 to 2240 g. CONCLUSIONS: Most preterm, low-birth-weight infants meet current eligibility criteria for hospital discharge at a postconceptional age of 35 to 37 weeks. This level of maturity is sufficiently predictive to serve as a convenient, easy-to-remember clinical marker for expected durations of hospital stay. For infants with birth weights of less than 1000 g, discharge at a post-conceptional age of 37 to 42 weeks is a more realistic expectation.

Effects of atropine in ponies with recurrent airway obstruction.

The effects of atropine on lung function and airway reactivity in two groups of ponies were measured. Principal ponies had a history of recurrent airway obstruction when housed in a barn and fed hay; control ponies had no history of airway obstruction. Principal and control ponies were paired, and measurements were made when principal ponies were in clinical remission (period A) and during an acute attack of airway obstruction (period B). Atropine did not alter pulmonary resistance (RL), dynamic compliance (Cdyn), or airway responsiveness in either group of ponies at period A or in the controls at period B. In principal ponies at period B, atropine did not alter Cdyn or the concentration of aerosol histamine required to decrease Cdyn to 65% of base line (ED65Cdyn) but reduced RL and the change in RL induced by 0.1 mg/ml histamine (delta RL0.1). It is likely that the latter observation was due to geometric changes in the airways, because the change in RL and in delta RL0.1 were significantly correlated. The results of this study show little resting bronchomotor tone in normal ponies, but a major portion of the increase in RL in principals at period B is mediated via muscarinic receptors. Little evidence exists for muscarinic receptor involvement in the response to aerosol histamine in either principal or control ponies.

Beta-adrenergic blockade in ponies with recurrent obstructive pulmonary disease.

Ponies with recurrent airway obstruction have hyperresponsive airways during acute disease exacerbations but not during clinical remission. We examined the effect of beta-adrenergic blockade with propranolol on airway responsiveness to aerosol histamine in six ponies with recurrent airway obstruction and six age- and gender-matched controls. Measurements were made with principal ponies in clinical remission (period A) and during an acute period of airway obstruction (period B). beta-Adrenergic blockade did not change airway responsiveness, dynamic compliance (Cdyn), or pulmonary resistance (RL) in either group of ponies at period A or in the control ponies at period B. In principal ponies at period B, propranolol significantly increased RL but was without effect on Cdyn or airway responsiveness. We conclude that the beta-adrenergic system is involved in the control of central airway caliber in principal ponies at period B but that this system does not seem to be involved in the mechanism of airway hyperresponsiveness to histamine.

Micropolyspora faeni causes airway inflammation but not hyperresponsiveness in sensitized ponies.

We assessed the effect of aerosol Micropolyspora faeni challenge in two groups of ponies by measuring lung function, airway reactivity to aerosol histamine, and bronchoalveolar lavage fluid cytology. One group of ponies was sensitized by subcutaneous injection of M. faeni in complete Freund's adjuvant, and the other group served as control. In both groups of ponies, measurements were made at base line and 5 h after aerosol administration of 30 ml of saline or 30 ml of 1% wt/vol particulate M. faeni antigen in saline. Saline challenge had no effect on any of the measured variables. M. faeni challenge had no effect on pulmonary mechanics or gas exchange in the control group but significantly increased respiratory frequency and minute ventilation and decreased arterial CO2 tension in the sensitized ponies. In both groups of ponies, aerosol M. faeni challenge significantly increased total white blood cell count and neutrophil numbers in bronchoalveolar lavage fluid while large mononuclear cell numbers decreased. Airway responsiveness was unaltered by saline or M. faeni challenge in both pony groups. We conclude that aerosol M. faeni challenge induces pulmonary neutrophilia and abnormalities of ventilation but is not accompanied by airway hyperresponsiveness in sensitized ponies.

Alpha 1-adrenergic-induced airway obstruction in ponies with recurrent pulmonary disease.

We examined the response of five ponies with recurrent airway obstruction (principals) and five age- and gender-matched controls to the aerosol alpha-adrenergic agonist phenylephrine after blockade with propranolol and atropine. Measurements were made with principal ponies in clinical remission (period A) and during acute airway obstruction (period B). The blockade had no effect on base-line pulmonary mechanics in control ponies during periods A and B or in the principal ponies during period A. However, in the principal ponies during period B, blockade increased dynamic compliance (Cdyn) and decreased pulmonary resistance (RL). Phenylephrine had no effect on the controls during either period. In the principals, phenylephrine decreased Cdyn and increased RL during both periods. The alpha 1-agonist aerosol prazosin shifted the phenylephrine dose-response curves to the right, but prasozin did not bronchodilate the principals during period B. This suggests that the role of alpha 1-adrenergic receptors in airway narrowing in ponies with recurrent airway obstruction is minimal. However, the response to phenylephrine in only the principal ponies suggests an increase in alpha-receptor numbers and/or activity in these animals compared with controls.

Injury to the ureter during laparoscopic tubal sterilization.

As the use of laparoscopy and laparoscopic tubal sterilization has increased, a number of serious complications have been reported. A case is described in which the ureter was damaged during laparoscopic sterilization. The majority of serious complications associated with laparoscopic sterilization have been burn injuries resulting from the use of cautery instruments. Thermal injuries are likely to occur when the operator is inexperienced, and when cautery instruments of the high-energy type are used. Meticulous technique is required in the performance of laparoscopic sterilization and low-energy "cold cautery" units should be used in this procedure.

Percutaneous endoscopic jejunostomy in a patient with previous esophagectomy.

Establishment of a percutaneous endoscopic jejunostomy via direct jejunal puncture was accomplished in a 45-year-old woman five years after a partial esophagectomy with cervical esophagogastrostomy for adenocarcinoma of the esophagus. The patient had recurrence of the cancer at the anastomotic site with subsequent inability to eat, necessitating a feeding tube for prolonged enteral nutrition. Although percutaneous puncture of the jejunum has been previously described, it has been limited to patients who had undergone partial or complete gastrectomies with Bilroth II anastomoses. This case report of direct endoscopic jejunal tube placement in a patient after esophagectomy further establishes this procedure as a viable alternative to surgically placed feeding tubes in patients with altered gastric anatomy.

Comparison of operative versus percutaneous endoscopic gastrostomy tube placement in the elderly.

To compare techniques of gastrostomy in elderly patients, the records of 100 patients age 70 and older who underwent gastrostomy tube placement as a primary procedure were reviewed. Two separate unmatched groups of 50 patients each were identified: those that underwent operative gastrostomy tube (OGT) placement and those that underwent percutaneous endoscopic gastrostomy tube (PEG) placement. The groups were studied for demographic similarities and for differences in morbidity, mortality, and ease of feeding. Comparison showed that PEGs had a lower mortality (0%) and morbidity (10%) than did OGTs where mortality was 4 per cent and morbidity was 22 per cent. PEGs began feeding sooner (1.0 day vs. 2.8 days) than OGTs. In addition, almost 60 per cent of the PEG patients underwent complete upper endoscopy at the time of the PEG, which revealed pathology that either altered the type of tube placed or the eventual medical management. PEG offers a less morbid, safer, and easier to use method of gastrostomy tube placement than OGT in the majority of elderly patients.

Resident education in surgical endoscopy.

Under the auspices of the Resident Education Committee of the Society of American Gastrointestinal Endoscopic Surgeons, 158 of 298 (53%) of surgical training program directors responded to a survey on the current status of endoscopy in residency programs. Although 100 per cent claim that gastrointestinal endoscopy is provided by their program, only 76 per cent have formal endoscopy training, usually centered around the PGY 3 level, with only 23 per cent having didactic lectures in endoscopy. Directors claim to have trained nearly all of their residents by the completion of residency, averaging 44 esophagogastroscopies, 37 colonoscopies, and 46 flexible sigmoidoscopies per resident. However, they feel only 71 per cent of trainees are able to perform esophagogastroscopies and 67 per cent to perform colonoscopies in clinical practice. Ninety-seven per cent of directors feel endoscopy is important to surgical residency training, and 87 per cent have full-time faculty doing endoscopy. Only 44 per cent have a director of endoscopy; endoscopy is supervised by surgeons exclusively in only 48 per cent. Only 35 per cent have ongoing endoscopy research. When surgeons are not performing endoscopy, 66 per cent feel that the gastrointestinal (GI) service provides adequate service or training. Gastroenterology has a monopoly in endoscopy at 28 per cent of institutions, and 67 per cent of program directors feel there would be resistance to the formation of a separate surgical endoscopy service. Surgeons work in their own surgical endoscopy suite in only 15 per cent of institutions; in a GI suite in 13 per cent; and in a combined suite in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous endoscopic gastrostomy. A mandate for complete diagnostic upper endoscopy.

One hundred patients underwent upper endoscopy for the placement of percutaneous endoscopic gastrostomies (PEGS) during a four year period from 1984 to 1988. These cases were retrospectively reviewed to document the need for total endoscopy during PEG. Ninety-seven per cent of the procedures were successful. In 89 per cent, a complete exam of the esophagus, stomach, and duodenum was performed, revealing pathologic findings in 59 per cent. The most common abnormalities were in the esophagus (23%) and the stomach (27%); however, a portion of the findings were also present in the duodenum (12%) and the pylorus (11%). Additional findings present in the complete esophagogastroduodenoscopy (EGD) done at the time of PEG included a five per cent incidence of gastric outlet obstruction and antral ulcers or polyps in six per cent. The breakdown of findings in the duodenum included eight per cent incidence of duodenal ulcers and four per cent incidence of duodenitis. A total of 22 per cent of the patients had some evidence of peptic ulcer disease. Many of the cases in which pathology was found required a change in medications and, when postoperative bleeding occurred after PEG, the other pathologic entity was much more likely to be the cause of the complication than the PEG. A careful and complete EGD is mandated every time a patient is scheduled for PEG.

Tracheostomy. A new indication for percutaneous endoscopic gastrostomy tube placement.

A review of patients undergoing elective tracheostomy (TRACH) and percutaneous endoscopic gastrostomy (PEG) was undertaken to decide whether addition of PEG to a planned tracheostomy was safe and indicated by conditions mandating the tracheostomy. Charts were reviewed for demographic data, details of operation, outcome, and disposition. Sixteen patients with an average age of 61 years were studied. Primary diagnosis included CNS disease (7), trauma (6), and multisystem failure (3). These patients had 35 associated diseases. Indications for tracheostomy were respiratory failure (9) and prolonged intubation (7). The average time from admission to procedure was 23.7 days. Average operative time was 50 minutes. There were three postoperative complications. Ten patients were discharged (5 home, 5 skilled facility) and six expired. All patients had functioning tracheostomies and PEGs at the time of disposition. Percutaneous endoscopic gastrostomy is a logical adjunct to planned tracheostomy, adding little morbidity but with potential benefit to long-term management in this special group of chronic care patients.

Single session panendoscopy. Indications and expectations for yield.

To assess the indications and yield of single session panendoscopy (SSPE), patients who underwent colonoscopy and esophagogastroduodenoscopy (EGD) at the same time were retrospectively reviewed. Endoscopy records and patient charts of 101 patients who underwent SSPE during a 45-month period were analyzed for demography, indication, and results. Average age was 72.9 years. Common indications were positive occult blood tests (74%), anemia (28%), altered bowel habits (15%), and iron deficiency (13%). Most frequent findings at colonoscopy included diverticulosis (47%), polyps (37%), hemorrhoids (28%), and arteriovenous (AV) malformations (13%). Nine cases of cancer were found, seven of which were right-sided. Colonoscopy was normal in 12 per cent. EGD findings include esophagitis (55%), hiatal hernia (47%), and gastritis (33%). Eleven per cent were normal. Occult blood loss is not predictive of either a positive or negative study. SSPE is a safe and specific approach; however, based on this study, colonoscopy is recommended as the initial study for occult blood loss with plans to proceed to EGD when the lower endoscopy is normal. Even when the colonoscopy suggests the etiology for occult blood loss, EGD will yield a significant number of treatable and unsuspected lesions.