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The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Cognitive control refers to the ability to produce flexible, goal-oriented behavior in the face of changing task demands and conflicting response tendencies. A classic cognitive control experiment is the Stroop-color naming task, which requires participants to name the color in which a word is written while inhibiting the tendency to read the word. By comparing stimuli with conflicting word-color associations to congruent ones, control processes over response tendencies can be isolated. We assessed the spatial specificity and temporal dynamics in the theta and gamma bands for regions engaged in detecting and resolving conflict in a cohort of 13 patients using a combination of high-resolution surface and depth recordings. We show that cognitive control manifests as a sustained increase in gamma band power, which correlates with response time. Conflict elicits a sustained gamma power increase but a transient theta power increase, specifically localized to the left cingulate sulcus and bilateral dorsolateral prefrontal cortex (DLPFC). Additionally, activity in DLPFC is affected by trial-by-trial modulation of cognitive control (the Gratton effect). Altogether, the sustained local neural activity in dorsolateral and medial regions is what determines the timing of the correct response.

Listening speech sounds activates motor and premotor areas in addition to temporal and parietal brain regions. These activations are somatotopically localized according to the effectors recruited in the production of particular phonemes. Previous work demonstrated that transcranial magnetic stimulation (TMS) of speech motor centers somatotopically altered speech perception, suggesting a role for the motor system. However, these effects seemed to occur only under adverse listening conditions, suggesting that degraded speech may stimulate listeners to adopt unnatural neural strategies relying on motor centers. Here, we investigated whether naturally occurring interspeaker variability, which did not affect task difficulty, made a speech discrimination task sensitive to TMS interference. In this paradigm, TMS over tongue and lips motor representations somatotopically altered the discrimination time of speech. Furthermore, the TMS-induced effect correlated with listeners' similarity judgments between listeners' and speakers' speech productions. Thus, the degree of motor recruitment depends on the perceived distance between listener and speaker. This result supports the claim that discriminating others' speech pattern requires the contribution of the listener's own motor repertoire. We conclude that motor recruitment in speech perception can be a natural product of discriminating speech in a normally variable and unpredictable environment, not merely related to task difficulty., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The treatment of solute addition, Na and water losses in hyperglycaemic hyponatraemia is guided by clinical judgement rather than by a quantitative assessment., Methods: We devised an iteration method to compute glucose appearance (G(A)) within the extracellular space, to obtain the PNa (plasma sodium concentration) expected by glucose addition only (PNa(G)). The difference between this and the actual measurement (PNa(1)) was used to compute the attending Na and/or volume depletion, and the PNa expected during correction. The equations were validated on computer-built models, where the electrolyte derangements were simulated, generating true values of plasma glucose (P(G)) and Na concentrations, from which surfeit and deficits were back-calculated with our formulas. We also computed G(A) and PNa(G) on 43 patients who were stratified into a group with normal hydration (PNa(1) = PNa(G)), one with prevalent Na depletion (PNa(1) < PNa(G)), and one with prevalent volume depletion (PNa(1) > PNa(G)). The volume conditions established by our computations were compared by logistic regression analysis with those assessed from clinical laboratory data., Results: The computer simulations demonstrated that the method gave exact results when only one variable changed, clinically useful estimates in the presence of mixed volume and sodium deficits. There was a strongly significant concordance between the clinical and the quantitative method (P < 0.001). The latter predicted the PNa measured after correction of hyperglycaemia (P < 0.001)., Conclusion: This new method more accurately computes the initial conditions, resulting in a useful stratification of patients which improves the quantitative evaluation and treatment of hyperosmolar coma.

Background: Angiotensin II (Ang II), arginine vasopressin (AVP) and tromboxane A(2) (TxA(2)) are dissimilar vasoconstrictors involved in regulating renal circulation. Whereas Ang II is primarily a physiological modulator, AVP and TxA(2) play important roles under pathological conditions. Previously, we have shown variable importance of intracellular Ca(2+) and protein kinase C for their mode of action (Ang II > AVP >U-46619), but the cell signalling via rho-associated kinase (ROK) is a common pathway. The aim of this study was to determine their sites of action in the renal vascular bed and the corresponding role of ROK at the microvascular level., Methods: Glomerular blood flow (GBF) and luminal diameter of different vessels (10-70 micro m) were measured in the split hydronephrotic kidney of anaesthetized rats. The tissue bath concentration of Ang II, AVP or the TxA(2) agonist U-46619 was adjusted to reduce GBF by approximately 50%. The measurements were repeated after adding a sub-maximal dose of the ROK inhibitor Y-27632 into the bath., Results: Ang II constricted all vessels significantly, the constriction being least in the proximal segment of the arcuate artery ( approximately 70 micro m). Significant constrictions due to AVP were found only in interlobular and arcuate arteries (20-70 micro m), but not in the afferent and efferent arterioles. U-46619 constricted only the arcuate artery (> or = 50 micro m). Y-27632 (10(-4) M) dilated all vessels significantly and increased GBF by 65%. Thereafter, effects of all agonists were severely attenuated. Control reductions in GBF could be obtained at higher concentrations of AVP (10-fold) and U-46619 (5-fold) and a lesser GBF reduction with Ang II (100-fold) without changes in the respective patterns of vascular constriction., Conclusions: Our data indicate that the agonists, in the order Ang II, AVP and TxA(2), constrict larger vessels within the renal vascular tree via activation of ROK. Therefore, ROK inhibitors may provide a therapeutic tool to antagonize pathological vasospasm of conduit vessels, which are resistant to other vasodilators.

Histologically detectable iron (HDI) and HFE mutations were searched for in liver biopsy specimens from 58 Italian patients with chronic hepatitis C, and morphologic features were compared to examine their reciprocal relation and their contribution to disease progression. HDI was evident in 48% of cases with features of nonhemochromatosis iron overload. Total, sinusoidal, and portal HDI increased with stage; grade was related to all iron scores because of the contribution of portal inflammation and interface hepatitis. HFE mutations were seen in 47% of patients with chronic hepatitis C and in 28% of control subjects; they were related to stage and the His63Asp mutation to portal HDI. On multivariate analysis, grade but not stage or HFE mutations was associated with HDI in all sites. Interface hepatitis with its sequelae (sinusoidal capillarization and microshunting) represents a major factor in iron deposition in chronic hepatitis C and justifies the features of HDI. HFE mutations are not responsible for HDI deposition but could favor the progression of virus-induced damage independently from interference with iron metabolism.

Increased insulinemic response to an oral glucose load has been demonstrated in Dahl salt-sensitive hypertensive rats. To determine whether this abnormality is mediated at the level of the insulin receptor, we compared insulin receptor binding and mRNA levels in tissues of Dahl salt-sensitive rats (DS) and in their normotensive controls, Dahl salt-resistant rats (DR). To evaluate possible influences of dietary sodium intake, rats were fed either low (0.07% NaCl) or high salt (7.5% NaCl) chow until the DS became hypertensive, and then were killed by decapitation. Fasting plasma glucose and plasma insulin levels did not differ between DR and DS rats and were not affected by salt intake. In response to an oral glucose load, plasma glucose had a similar increase in DR and DS rats, but the increase in plasma insulin was significantly greater in DS rats. Scatchard analysis of binding was obtained from in situ autoradiographic studies performed in frozen skeletal muscle and kidney sections, and insulin receptor mRNA levels were measured by slot-blot hybridization. Number and affinity of insulin receptors were comparable in skeletal muscle and kidney of DR and DS rats and, in both groups, binding parameters were not affected by dietary sodium chloride. Hepatic and renal insulin receptor mRNA levels were also comparable in DR and DS rats fed either low or high salt chow. Thus, increased plasma insulin response to oral glucose load is associated with normal insulin receptor binding and gene expression in peripheral tissues in rats with Dahl hypertension. A postreceptor defect is likely responsible for the decreased sensitivity to insulin in this model of genetic hypertension.

Two patients with chronic sialoadenitis had features of Bartter's and Gitelman's syndrome, respectively. The main complaints were leg paraesthesiae and acute arthritis. A good response to oral K+ supplementation, allopurinol and low-dose prednisone was obtained. The features of Sjögren's-related renal diseases are reviewed.

To investigate the relationships between the sympathetic nervous system (SNS) and parameters of glucose metabolism in arterial hypertension, daily urinary excretion of catecholamines and plasma glucose, insulin, and C-peptide response to an oral glucose load (OGL) have been evaluated in 77 untreated patients with mild-to-moderate essential hypertension and in 31 normotensive controls. Urinary excretion of norepinephrine (UNE) was positively correlated with body mass index and with plasma glucose levels both at fast and after OGL. No correlations were found between urinary excretion of catecholamines and plasma insulin and C-peptide levels both at fast and in response to OGL. Because the frequency distribution of UNE was bimodal, hypertensive subjects were separated into two subgroups using an arbitrary cutoff, and the parameters of glucose metabolism were compared. Subjects with UNE > 205 microg/day had greater levels of fasting glucose and greater glycemic response to OGL than subjects with UNE < 205 microg/day, whereas no significant differences between the groups were found in fasting and stimulated plasma insulin and C-peptide. Thus, activation of SNS is related to glucose tolerance but not hyperinsulinemia and insulin hypersecretion in essential hypertension. Plasma glucose levels, independent of insulin, may contribute to the relationship between SNS activity and blood pressure in essential hypertension.

Background: We wanted to validate by direct measurements in rat tubules a technique used to calculate segmental volume absorption by each segment of the human nephron., Methods: Experiments were performed on 17 rats during hypertonic Na infusion prior to and after frusemide administration. Tubular samples were taken from early distal and last proximal sites. The rate of filtration of single nephrons (SNGFR) was calculated by the technique of total collection of tubular fluid using labelled inulin as a marker. Reabsorption was computed by the tubular fluid to plasma (TF/P) inulin concentration ratio., Results: SNGFR was 50 +/- 4 nl/min at the distal (n = 82), 51 +/- 3 nl/min at the proximal sampling site (n = 112, P > 0.65) during baseline conditions. Percent reabsorptions were 85 +/- 1 and 69 +/- 2% respectively (P < 0.0001). During frusemide these values were 52 +/- 6 nl/min and 76 +/- 2% at the distal, 49 +/- 5 nl/min and 66 +/- 2% at the proximal site. In 83 paired proximal collections, fractional (68 +/- 1 versus 67 +/- 1% P > 0.32), absolute reabsorption (34 +/- 2 versus 33 +/- 2, P > 0.50) and SNGFR (50 +/- 2 nl/min versus 50 +/- 3 nl/min, P > 0.99) were not different between baseline and frusemide. In 25 re-collections from the distal tubule these same values were 83 +/- 2% versus 76 +/- 2%, and 48 +/- 4 nl/min versus 55 +/- 6 nl/min respectively. Very similar results were obtained in 55 paired distal-proximal collections during baseline and 42 such pairs during frusemide. In the presence of the diuretic the fractional urine excretion was significantly correlated (R = 0.83, P < 0.0001) with fractional proximal delivery, Na+ resorption by Henle's loop was 22 +/- 2% calculated from clearance data and 23 +/- 1% of GFR from micropuncture data respectively. They were not significantly different (P > 0.70) and were significantly correlated (R = 0.57, P < 0.02)., Conclusions: These data demonstrate that frusemide does not act proximally and that delivery beyond the proximal tubule approximates urine flow rate during the action of the drug. The values of segmental reabsorption along the nephron computed on clearance measurements are superimposable upon those obtained directly by micropuncture.

Background: We wanted to verify whether the calculations of segmental tubular reabsorption obtained during water diuresis were supported by direct micropuncture measurements., Methods: Experiments were performed on 18 rats during baseline water diuresis (B) and after the administration of frusemide (F), 10 mg/kg, by whole-kidney clearance measurements and micropuncture collections from early distal (ED) and last proximal (LP) tubular segments., Results: GFR was 957+/-79 in B, 1053+/-77 microl/min in F, P>0.013. SNGFR was 38+/-1 in 166 and 38+/-1 nl/min in 165 tubules respectively, P>0.77. In LP collections the percentage reabsorption was 71+/-2 in B and 76+/-2% during F (P>0.07) in 99 and 95 samples respectively. The absolute proximal reabsorption was not changed by F (27.6+/-1.5 versus 27.7+/-1.3 nl/min, P>0.96) The data were superimposable when the analysis was restricted to paired data. The difference between ED and LP resorption was 17+/-3 during B and fell significantly (P<0.008) to 5+/-3% during F, measured by clearance techniques, and the percentage of GFR excreted during F, measured by clearance techniques, and the percentage delivery of filtrate beyond the proximal tubule, measured independently by micropuncture, were not different (27+/-2 versus 24+/-2%, P>0.10), while they were significantly correlated (P<0.04). The calculations of segmental Na reabsorption along the different nephron segments by clearance techniques were not significantly different from and were significantly correlated with the reabsorptions measured directly by micropuncture., Conclusions: The present experiments validate the calculations of reabsorption by techniques applicable to human studies of clinical physiology.

An immunocompetent man developed malaise, fever, progressive weight loss, eosinophilia, and transient pulmonary infiltrates that responded to steroid treatment but recurred after its discontinuation. Examinations of feces, bronchoalveolar lavage fluid, and pulmonary tissue obtained during a 50-day period of hospitalization yielded negative results. When a new bronchoalveolar lavage sample and a new pulmonary biopsy specimen showed nematode larvae and adult worms, treatment with thiabendazole was started. However, therapy with this agent and then with mebendazole had no impact on the patient's downhill course, which ended in respiratory distress and death. Autopsy documented an overwhelming pulmonary infection with a metastrongylid nematode resembling a species of Angiostrongylus. Histologic study revealed features of necrotizing angiitis closely mimicking those of Wegener's granulomatosis. To our knowledge, this is the first reported instance of patent metastrongylid parasitism of the human pulmonary arteries with necrotizing angiitis caused by a reaction to the parasite and/or its metabolic products.

The authors measured immunoenzymatically circulating intercellular adhesion molecule-1 (cICAM-1) concentration in 135 patients with liver disease of either viral or toxic etiology: 13 had acute hepatitis; 58 had mild chronic liver disease; and 64 had cirrhosis (superimposed in 30 by hepatocellular carcinoma). Forty patients with extrahepatic diseases (19 with malignancies) and 28 healthy blood donors were tested as controls. One-way analysis of variance demonstrated a significant variability of cICAM-1 concentration among groups (F = 76.67, P < .0001), the highest value being recorded in acute hepatitis (Bonferroni's test for pairwise comparisons, P < .01). Total bilirubin showed a strong correlation with cICAM-1 (R = 0.766, P < .001). By stepwise multiple regression analysis the independent predictors of cICAM-1 concentration were chosen in the following order: total bilirubin; aspartate aminotransferase; cholinesterase; alpha-1-antitrypsin; and immunoglobulins. Thus, in addition to inflammation, cholestasis and decline of functioning hepatic mass may influence cICAM-1 concentration.

An 18-year-old-woman, with dermatitis herpetiformis, acute glomerulonephritis, malabsorption and villous atrophy due to massive infiltration of IgA producing plasma cells was studied. By light microscopy, her renal biopsy specimen showed heavy immunofluorescence for IgA, a mixed proliferative and membranous lesion with occasional crescents and focal sclerosis. Electron microscopic examination revealed three main lesions: (1) swelling and bleb formation in endothelial cells, (2) extensive fusion of foot processes of podocytes, and (3) a dense quasi-linear, continuous deposition of immune complexes, encompassing several loops; they were characteristically located within the basement membrane at the boundary between the lamina densa and the lamina rara interna. At occasional points where the immune complexes had reached the outer aspects of the basement membrane, there was damage to the podocyte cytoplasm. This electron microscopic aspect supports the interpretation that these immune complexes, although non-complement fixing, exhibit a high damaging potential, leading to relentless disease progression.

A patient who had diffuse lymph node enlargement, fever, skin rashes, anemia and polyclonal hypergammaglobulinemia is described. Histologic examination of lymph nodes taken from different sites (cervical, axillary and inguinal) revealed the presence of giant lymph node hyperplasia. The liver and bone marrow showed a moderate lymphocytic and plasma cell infiltration. The clinical presentation of a multicentric variety of giant lymph node hyperplasia in the reported case is similar to the clinical features usually associated with angio-immunoblastic lymphadenopathy with dysproteinemia, indicating that these two disorders may be related and may affect the same organs and systems. Alternatively, this histologic reactive giant lymph node hyperplasia progressing with a rapid declivitous course can be considered distinctive of a separate entity.