The influence of inter-regional delays in generating large-scale brain networks of phase synchronization.

Large-scale networks of phase synchronization are considered to regulate the communication between brain regions fundamental to cognitive function, but the mapping to their structural substrates, i.e., the structure-function relationship, remains poorly understood. Biophysical Network Models (BNMs) have demonstrated the influences of local oscillatory activity and inter-regional anatomical connections in generating alpha-band (8-12 Hz) networks of phase synchronization observed with Electroencephalography (EEG) and Magnetoencephalography (MEG). Yet, the influence of inter-regional conduction delays remains unknown. In this study, we compared a BNM with standard "distance-dependent delays", which assumes constant conduction velocity, to BNMs with delays specified by two alternative methods accounting for spatially varying conduction velocities, "isochronous delays" and "mixed delays". We followed the Approximate Bayesian Computation (ABC) workflow, i) specifying neurophysiologically informed prior distributions of BNM parameters, ii) verifying the suitability of the prior distributions with Prior Predictive Checks, iii) fitting each of the three BNMs to alpha-band MEG resting-state data (N = 75) with Bayesian optimization for Likelihood-Free Inference (BOLFI), and iv) choosing between the fitted BNMs with ABC model comparison on a separate MEG dataset (N = 30). Prior Predictive Checks revealed the range of dynamics generated by each of the BNMs to encompass those seen in the MEG data, suggesting the suitability of the prior distributions. Fitting the models to MEG data yielded reliable posterior distributions of the parameters of each of the BNMs. Finally, model comparison revealed the BNM with "distance-dependent delays", as the most probable to describe the generation of alpha-band networks of phase synchronization seen in MEG. These findings suggest that distance-dependent delays might contribute to the neocortical architecture of human alpha-band networks of phase synchronization. Hence, our study illuminates the role of inter-regional delays in generating the large-scale networks of phase synchronization that might subserve the communication between regions vital to cognition.

Modules in connectomes of phase-synchronization comprise anatomically contiguous, functionally related regions.

Modules in brain functional connectomes are essential to balancing segregation and integration of neuronal activity. Connectomes are the complete set of pairwise connections between brain regions. Non-invasive Electroencephalography (EEG) and Magnetoencephalography (MEG) have been used to identify modules in connectomes of phase-synchronization. However, their resolution is suboptimal because of spurious phase-synchronization due to EEG volume conduction or MEG field spread. Here, we used invasive, intracerebral recordings from stereo-electroencephalography (SEEG, N = 67), to identify modules in connectomes of phase-synchronization. To generate SEEG-based group-level connectomes affected only minimally by volume conduction, we used submillimeter accurate localization of SEEG contacts and referenced electrode contacts in cortical gray matter to their closest contacts in white matter. Combining community detection methods with consensus clustering, we found that the connectomes of phase-synchronization were characterized by distinct and stable modules at multiple spatial scales, across frequencies from 3 to 320 Hz. These modules were highly similar within canonical frequency bands. Unlike the distributed brain systems identified with functional Magnetic Resonance Imaging (fMRI), modules up to the high-gamma frequency band comprised only anatomically contiguous regions. Notably, the identified modules comprised cortical regions involved in shared repertoires of sensorimotor and cognitive functions including memory, language and attention. These results suggest that the identified modules represent functionally specialised brain systems, which only partially overlap with the brain systems reported with fMRI. Hence, these modules might regulate the balance between functional segregation and functional integration through phase-synchronization.

Long-range phase synchronization of high-frequency oscillations in human cortex.

Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100-400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se.

[The computerized outpatient management of subjects at neoplastic risk]. / Gestione ambulatoriale computerizzata di soggetti a rischio neoplastico.

The authors reviewed literature data regarding risk factors of cancer in order to produce a software that could identify asymptomatic subjects at "neoplastic risk" by means of the analysis of the relative risk (RR) of each factor of his/her life-style. More in detail, the relationship between diet and cancer, tobacco use, alcohol consumption, sexual behaviour, parity and other obstetric-gynecologic aspects, medications, occupational hazards, environmental pollution and genetic susceptibility were reviewed. A complex multi-parametric evaluation system was realized to calculate risk of cancers through computerized elaboration. The program operates on anamnestic, objective and instrumental data derived from a clinical data-base.

[A retrospective study on the efficacy of the treatment of functional dyspepsia. An evaluation of 166 cases]. / Studio retrospettivo sull'efficacia del trattamento della dispepsia funzionale. Valutazione di 166 casi.

A retrospective study is reported carried out on a group of 166 patients affected by dyspeptic syndrome who presented at least 3 of the 9 symptoms which characterise this pathology. One hundred and twenty-eight patients underwent prokinetic drug therapy and 38 received placebo. Clinical parameters were evaluated following one month of therapy all patients in order to compare them to basal values. The results obtained confirm a satisfactory efficacy of the prokinetic treatment in improving dyspeptic symptoms. Although administered to a smaller number of patients, placebo was also found to play an important role in the multifactorial etiopathogenesis of the dyspeptic syndrome on a functional basis.

[A comparative evaluation of computerized diagnostic decisional support in gastroenterology in relation to typical clinical pictures]. / Valutazione comparativa di un supporto decisionale diagnostico computerizzato in gastroenterologia in rapporto alla tipicità dei quadri clinici.

On the basis of the results obtained in a previous perspective comparative study aimed to compare the diagnostic accuracy of a computerized diagnostic decisional support in gastroenterology with that of non-specialist physicians, the Authors have carried out a retrospective study, based on the same series and on the same results, but disaggregating the global comparisons according to the feature of the clinical presentations. The latter were therefore classified by independent gastroenterologists as "typical", "atypical", or "borderline", and for each group the difference of diagnostic accuracy between program and physicians was again evaluated. Even if the program proved more accurate in all groups, the greatest difference was observed in the "borderline" group which the Authors claim to include the kind of presentation which more than any other needs a decisional aid. This should suggest a possible useful implementation of the system in daily clinical practice.

[Computerized dynamic endothermography of the gastrointestinal mucosa as an indirect index of the state of vascularization of the abdominal organs. A preliminary note]. / L'endotermografia dinamica computerizzata della mucosa gastrointestinale quale indice indiretto dello stato di vascolarizzazione degli organi addominali. Nota preliminare.

Computerized Dynamic Endothermy (CDE) has been applied to the evaluation of the gastroenteric microcirculation. This new method enables mucosal temperature changes to be detected in a dynamic and functional way. With preventive induction of a temperature change (cold stimulus), the instrument measures the time required for the establishment of previous mucosal temperature. Computerized data are displayed in the form of a time/temperature curve. Results obtained on rabbits showed, during ischaemic conditions, a greater reduction of gastric layer temperature during cold stimulus than in basal conditions, followed by a slower return to basal temperature during the recovery time.

Clinical application of a computerized diagnostic aid in the initial evaluation of 250 outpatients with gastrointestinal complaints.

The results of a prospective controlled study designed to evaluate the performance of a computerized diagnostic aid in the clinical setting are reported herein. Two hundred and fifty patients referred to an outpatient clinic for gastrointestinal complaints were entered into the study. The diagnostic aid program was used routinely and the findings elicited from patients' medical histories and physical examinations were entered into the computer at the time of initial evaluation. The accuracy of the program's diagnoses was measured and compared with the accuracy of diagnoses made by a control group of physicians. The overall diagnostic accuracy of the program was found to be 69.2% (P much less than .0000001), a value significantly greater (P = .0005) than the overall accuracy of the control group of physicians, which was found to be 52%. A high agreement rate between program and physicians was also observed. These preliminary results seem to indicate a practical use for the program as a support in the initial screening of patients presenting with gastrointestinal complaints.

Treatment of esophageal anastomotic leakages after cancer resection. The role of total parenteral nutrition.

A series of 16 cases of esophageal anastomotic leakages after cancer resection observed from 1978 to 1982 is analyzed in a retrospective manner. Eight patients related to the period 1978 to 1980 (series A) were treated with emergency surgery while the remaining eight patients observed from 1980 to 1982 (series B) were treated conservatively with total parenteral nutrition (TPN) and complete fasting. Seven patients from series A eventually died postoperatively and one patient had a good recovery after emergency reintervention. In the series B six patients left the hospital with complete healing of the anastomotic leaks after 27.2 +/- 13.5 days of TPN and complete fasting, while failure of the treatment was observed in two patients who died from septic mediastinitis and acute respiratory failure. Different incidence of positive clinical results in Series A and B was statistically significant (p less than 0.01). The role of TPN and complete fasting will be discussed as the primary approach for the management of this severe complication, taking in consideration the suture line drainage and the control of infection.

Colon motility and colo-anal reflexes in chronic idiopathic constipation. Effects of a novel enterokinetic agent cisapride.

Motor activity of the colon and reflex behaviour of the anal sphincters in normal subjects and in patients with idiopathic constipation were studied using a novel probe with 5 open-end tips to measure pressures, and 3 balloons for stimulation of the distal colon. Constipation appeared to be associated with an increased threshold of the inhibitory relaxation reflex of the internal anal sphincter (41.7 in normals and 65.7 in patients), and in particular with a blunted sensation of the defaecation urge (51.0 in normals and 112.8 in patients). Single-blind comparison with a placebo showed that cisapride, a new gastrointestinal prokinetic substance, had a significant effect on the sensation threshold, which normalized or improved in 15 out of the 16 patients studied.

Immunosuppressive effect of surgery evaluated by the multitest cell-mediated immunity system.

The immunosuppressive effect of surgery in a series of 100 elective laparotomies was determined by analysing the delayed skin hypersensitivity, the most sensitive in-vivo reflection of cell-mediated immunity. For this purpose, a new method (Multitest cell-mediated immunity system) for simultaneous, multiple, intradermal skin tests was used. This system uses a plastic disposable device for simultaneous intradermal injection of seven immunologically standardized recall antigens, offering the possibility of assessing a patient's immunologic capability in a manner that is painless, rapid, safe, reproducible and quantifiable. Patients were tested preoperatively and on days 1, 3 and 7 after operation. Twenty healthy volunteers, the control group, were similarly tested. Immunosuppression was observed in all patients, reaching a peak on postoperative day 3. Recovery occurred between 7 and 10 days after operation. Immunosuppression was more severe and prolonged in patients with neoplastic disease. By continued immunologic monitoring using the Multitest system, the authors could confirm the suggested immunosuppressive effect of operation and establish that the phenomenon is temporary.

[Degree of parietal penetration of gastric cancer in relation to medium- and long-term survival]. / Il grado di penetrazione parietale del cancro gastrico in relazione alla sopravvivenza a medio e lungo termine.

The Authors analysed their experience about gastric carcinoma, with particular reference to short, middle and long time survival in relation to the degree of parietal penetration. In the patients without remote metastases, the survival till 5 years depends mainly on this factor, whereas the lymphonodal spreading plays a secundary rôle, especially in the cases where the tumour deeply infiltrated the gastric wall. Lymphoadenectomy, therefore, seems essential in cases of neoplasm with low degree of parietal penetration, whereas in those with high degree it does not seem determinant on the remote results.

[Evaluation of the functional modifications of the lower esophageal sphincter after use of the Angelchik prosthesis]. / Valutazione delle modificazioni funzionali dello sfintere esofageo inferiore (LES) dopo applicazione della protesi di Angelchik.

The manometric recording of Lower Esophageal Sphincter (LES) has been made in 8 patients who have undergone surgical apposition of Angelchik prosthesis for hiatal hernia. The patients underwent an esophageal manometric study in the preoperative period, one month and one year after the intervention. In the preoperative patients, the mean LES pressure was 10,3 +/- 0,5 mmHg and there was sphincterial incoordination to peristaltic waves after swallow. In one month postoperative patients the LESP was 20,1 +/- 1,0 mmHg (p less than 0,001), and one year after the LESP was 17,0 +/- 0,3 (p less than 0,001) with an ameliorated coordination of the LES activity in response to swallow. Therefore, during postoperative manometric controls the Authors identified a high pressure subdiaphragmatic zone unmodified by deglutitory acts which was not present in the preoperative investigation. Probably the presence of this zone would been explained as a consequence of mechanical action of the prosthesis and the postsurgical fibrino-reaction around the prosthesis. The Authors discussed the results obtained and their importance to Angelchik prosthesis employment for surgical correction of hiatal hernia.

[Controlled clinical study of the action of mebeverine hydrochloride in the treatment of irritable colon]. / Studio clinico controllato sulla azione del cloridrato di mebeverina nel trattamento del colon irritabile.

The results of a study about the mebeverina administered in 45 cases of irritable colon are reported. The clinical and laboratory findings together with the results of colometrography under psychic stimulation, have shown the therapeutic efficacy of the new formulation, specially in irritable colon with abdominal pain. Its tolerance was excellent.