Rehabilitation Modulates High-Order Interactions Among Large-Scale Brain Networks in Subacute Stroke.

The recovery of motor functions after stroke is fostered by the functional integration of large-scale brain networks, including the motor network (MN) and high-order cognitive controls networks, such as the default mode (DMN) and executive control (ECN) networks. In this paper, electroencephalography signals are used to investigate interactions among these three resting state networks (RSNs) in subacute stroke patients after motor rehabilitation. A novel metric, the O-information rate (OIR), is used to quantify the balance between redundancy and synergy in the complex high-order interactions among RSNs, as well as its causal decomposition to identify the direction of information flow. The paper also employs conditional spectral Granger causality to assess pairwise directed functional connectivity between RSNs. After rehabilitation, a synergy increase among these RSNs is found, especially driven by MN. From the pairwise description, a reduced directed functional connectivity towards MN is enhanced after treatment. Besides, inter-network connectivity changes are associated with motor recovery, for which the mediation role of ECN seems to play a relevant role, both from pairwise and high-order interactions perspective.

No Difference in Muscle Basal Oxygenation in a Bedridden Population Pre and Post Rehabilitation.

Long periods of bed rest for elderly population, due to a femur fracture event, can cause a deterioration in the muscular capacity. Therefore, monitoring of the muscle oxidative capacity in this fragile population is necessary to define the muscular oxidative metabolism state before and after a rehabilitation period. The time-domain near-infrared spectroscopy (TD-NIRS) technique enables the absolute values to be calculated for hemodynamic parameters such as oxy- (O2Hb), deoxy- (HHb), total- (tHb) haemoglobin, and tissue oxygen saturation (SO2) of the muscular tissue. In this work, we have characterized vastus lateralis muscle hemodynamics during a baseline period at two different time points: after the surgery (PRE) and after 15 days of rehabilitation (POST). The mean values for the absolute values of the hemodynamic parameters were: O2Hb_PRE = 49.1 ± 14.1 µM; O2Hb_POST = 47.1 ± 13.4 µM; HHb_PRE = 28.3 ± 10.3 µM; HHb_POST = 26.7 ± 9.9 µM; tHb_PRE = 77.3 ± 23.6 µM; tHb_POST = 73.8 ± 21.4 µM; SO2_PRE = 63.9 ± 4.0% and SO2_POST = 64.9 ± 5.6%. The hemodynamic parameters did not show significant differences at both group and single subject level. These results suggest that for this kind of population, the baseline of the hemodynamic parameters is not the best one to consider to assess the rehabilitation progresses in terms of muscular oxidative metabolism.

Role of the EEG Theta Network During Software Production: A Connectivity Study.

Software programming is an acquired evolutionary skill originating from consolidated cognitive functions (i.e., attentive, logical, coordination, mathematic calculation, and language comprehension), but the underlying neurophysiological processes are still not completely known. In the present study, we investigated and compared the brain activities supporting realistic programming, text and code reading tasks, analyzing Electroencephalographic (EEG) signals acquired from 11 experienced programmers. Multichannel spectral analysis and a phase-based effective connectivity study were carried out. Our results highlighted that both realistic programming and reading tasks are supported by modulations of the Theta fronto-parietal network, in which parietal areas behave as sources of information, while frontal areas behave as receivers. Nevertheless, during realistic programming, both an increase in Theta power and changes in network topology emerged, suggesting a task-related adaptation of the supporting network system. This reorganization mainly regarded the parietal area, which assumes a prominent role, increasing its hub functioning and its connectivity in the network in terms of centrality and degree.

Comparison between directed causal flow metrics for the assessment of resting-state EEG motor network connectivity in subacute stroke patients.

Isolated effective coherence (iCoh) is a measure of neural causal functional connectivity from EEG signals that was proven to overperform the Generalized Partial Directed Coherence (gPDC). However, iCoh sensitivity in the identification of reliable functional neural connections with respect to random links was not investigated. This study aims to compare the sensitivity of iCoh and gPDC with a statistical surrogates' approach. The cerebral motor network topology of a cohort of subjects in sub-acute stage after stroke was investigated. iCoh showed enhanced statistical discriminative power of the relevant connections within the motor network with respect to gPDC. This property influenced the assessment of ipsilesional intra-hemispheric topographic variations occurring in the population after a physical rehabilitation program.

Monitoring the haemodynamic response to visual stimulation in glaucoma patients.

In this paper, we used time-domain functional near infrared spectroscopy (TD-fNIRS) to evaluate the haemodynamic response function (HRF) in the occipital cortex following visual stimulation in glaucomatous eyes as compared to healthy eyes. A total of 98 subjects were enrolled in the study and clinically classified as healthy subjects, glaucoma patients (primary open-angle glaucoma) and mixed subjects (i.e. with a different classification for the two eyes). After quality check data were used from HRF of 73 healthy and 62 glaucomatous eyes. The amplitudes of the oxygenated and deoxygenated haemoglobin concentrations, together with their latencies with respect to the stimulus onset, were estimated by fitting their time course with a canonical HRF. Statistical analysis showed that the amplitudes of both haemodynamic parameters show a significant association with the pathology and a significant discriminating ability, while no significant result was found for latencies. Overall, our findings together with the ease of use and noninvasiveness of TD-NIRS, make this technique a promising candidate as a supporting tool for a better evaluation of the glaucoma pathology.

Sustained fatigue assessment during isometric exercises with time-domain near infrared spectroscopy and surface electromyography signals.

The effect of sustained fatigue during an upper limb isometric exercise is presented to investigate a group of healthy subjects with simultaneous time-domain (TD) NIRS and surface electromyography (sEMG) recordings on the deltoid lateralis muscle. The aim of the work was to understand which TD-NIRS parameters can be used as descriptors for sustained muscular fatigue, focusing on the slow phase of this process and using median frequency (MF) computed from sEMG as gold standard measure. It was found that oxygen saturation and deoxy-hemoglobin are slightly better descriptors of sustained fatigue, than oxy-hemoglobin, since they showed a higher correlation with MF, while total-hemoglobin correlation with MF was lower.

8-substituted adenosine and theophylline-7-riboside analogues as potential partial agonists for the adenosine A1 receptor.

A series of 8-substituted adenosine and theophylline-7-riboside analogues (28 and 9 compounds, respectively) was tested on adenosine A1 and A2A receptors as an extensive exploration of the adenosine C8-region. Alkylamino substituents at the 8-position cause an affinity decrease for adenosine analogues, but an affinity increase for theophylline-7-riboside derivatives. The affinity decrease is probably due to a direct steric hindrance between the C8-substituent and the binding site as well as to electronic effects, not to a steric influence on the ribose moiety to adopt the anti conformation. The 8-substituents increase the affinity of theophylline-7-riboside analogues probably by binding to a lipophilic binding site. The intrinsic activity was tested in vitro for some 8-substituted adenosine analogues, by determining the GTP shift in receptor binding studies and the inhibition of adenylate cyclase in a culture of rat thyroid FRTL-5 cells, and in vivo in the rat cardiovascular system for 8-butylaminoadenosine. Thus, it was shown that 8-ethyl-, 8-butyl-, and 8-pentylamino substituted analogues of adenosine may be partial agonists in vitro, and that 8-butylaminoadenosine is a partial agonist for the rat cardiovascular A1 receptor in vivo.

Characterization of ecto-ATPase on human blood cells. A physiological role in platelet aggregation?

Ecto-ATPase (EC 3.6.1.15) is a plasma membrane-bound enzyme which degrades extracellular triphosphate nucleotides. Although its physiological function is still unclear, the enzyme obscures the study of P2 purinoceptors (i.e. receptors for ATP and other di- and triphosphate nucleotides), since it is capable of metabolizing the pharmacological ligands, such as ATP, for these receptors. We characterized the ecto-ATPase activity on human blood cells with a [gamma 32P]ATP assay and HPLC measurements. We also determined whether ecto-ATPase activity could affect the anti-aggregatory role of ATP in whole human blood. The Km for ATP of the ecto-ATPase on human blood cells was 8.5 +/- 2.3 microM and the maximum degradation rate, at 37 degrees, was 2.7 +/- 1.1 nmol ATP/(min x mL whole blood). In whole blood the major part of ATP was broken down by the blood cells, predominantly by the leukocytes. ATP and UTP were broken down equally well, mainly yielding the corresponding di- and monophosphates. In search of inhibitors for the ecto-ATPase, we studied several analogs of ATP. 8-Bromo-ATP as well as 2'- and 3'-deoxy-ATP were substrates for the enzyme. In contrast, modification of the phosphate side chain yielded inhibitors. Subsequently, a possible role of the ecto-ATPase in platelet aggregation was verified. To assess the role of the plasma membrane-bound enzyme, platelet aggregation was determined in whole blood instead of platelet-rich plasma. In the presence of ATP alone, an antagonist of ADP-induced platelet aggregation, some aggregation was still observed. As breakdown of ATP by the ecto-ATPase leads to gradual formation of ADP, as mentioned above, we compared the effects of a stepwise versus bolus addition of ADP. Subsequent dosing of ADP (1.5, 2.5, 5 and 10 microM) resulted in platelet aggregation but to a much smaller extent, at most approximately 60%, compared to the amount of platelet aggregation obtained with a bolus addition of ADP (10 microM). In conclusion, human blood cells possess a high affinity ecto-ATPase which degrades ATP as well as ATP analogs with modified base and ribose moieties. ATP analogs with a modified phosphate chain are inhibitors of the ecto-ATPase. A direct role of the ecto-ATPase activity on platelet aggregation is probably small, as degradation of ATP to ADP proceeds slowly and cumulative addition of ADP to platelets in whole blood results in a modest amount of aggregation.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of nucleoside uptake in human erythrocytes by a new series of compounds related to lidoflazine and mioflazine.

The zero-trans influx of uridine in human erythrocytes is inhibited by lidoflazine and analogs thereof. The concentrations required for inhibition of nucleoside transport were higher when the compounds were simultaneously added with uridine than upon preincubation of the inhibitors with the erythrocytes. R70380 proved to be the most active compound in this respect, its IC50 value being 13 nM after preincubation. Even the reference compounds nitrobenzylthioinosine and dilazep were remarkably more potent with preincubation; dipyridamole, however, was not.

Influence of the molecular structure of N6-(omega-aminoalkyl)adenosines on adenosine receptor affinity and intrinsic activity.

The affinities of a series of N6-(omega-aminoalkyl)adenosines as probes for A1 and A2 adenosine receptors were determined in various radioligand binding assays and the intrinsic activities were measured in adenylate cyclase assays. Clear species differences were noticed for A1 receptor affinity of these adenosine receptor agonists, the compounds being more active in calf than in rat brain tissue. The affinity profile within the series was, however, rather similar in both membrane preparations, with N6-9-aminononyladenosine displaying highest affinity. The A2 receptor affinities were comparable to values measured for the A1 receptor in its low affinity state, as assessed with a radiolabelled antagonist in the presence of 1 mM GTP. Calculation of the intrinsic activities of the adenosine analogues from their modulating action on adenylate cyclase showed almost all the compounds to be equally effective to (-)-N6-(R-phenylisopropyl) adenosine, on either A1 or A2 adenosine receptors. N6-3-Aminopropyl- and N6-12-aminododecyladenosine, however, proved to be partial agonists, the first on A1 and the second on A2 adenosine receptors. The data are used as the basis for a discussion of adenosine receptor subtype selectivity and intrinsic activity in general.

The combined use of high-performance liquid chromatography and radioimmunoassay for the bioanalysis of nicomorphine and its metabolites.

Methods have been developed for the determination of nicomorphine using reversed-phase HPLC with UV detection; for the simultaneous assay of morphine and mononicotinoylmorphine by a coupled normal-phase HPLC-radioimmunoassay method; and for conjugates of morphine and mononicotinoylmorphine by radioimmunoassay. The methods have been evaluated and applied to a pharmacokinetic study of nicomorphine administered intramuscularly.