Neural oscillations during motor imagery of complex gait: an HdEEG study

The aim of this study was to investigate differences between usual and complex gait motor imagery (MI) task in healthy subjects using high-density electroencephalography (hdEEG) with a MI protocol. We characterized the spatial distribution of alpha- and beta-bands oscillations extracted from hdEEG signals recorded during MI of usual walking (UW) and walking by avoiding an obstacle (Dual-Task, DT). We applied a source localization algorithm to brain regions selected from a large cortical-subcortical network, and then we analyzed alpha and beta bands Event-Related Desynchronizations (ERDs). Nineteen healthy subjects visually imagined walking on a path with (DT) and without (UW) obstacles. Results showed in both gait MI tasks, alpha- and beta-band ERDs in a large cortical-subcortical network encompassing mostly frontal and parietal regions. In most of the regions, we found alpha- and beta-band ERDs in the DT compared with the UW condition. Finally, in the beta band, significant correlations emerged between ERDs and scores in imagery ability tests. Overall we detected MI gait-related alpha- and beta-band oscillations in cortical and subcortical areas and significant differences between UW and DT MI conditions. A better understanding of gait neural correlates may lead to a better knowledge of pathophysiology of gait disturbances in neurological diseases

Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells

A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 mM, and 0.29e12.2 mM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK

Locally advanced prostate cancer: three-dimensional magnetic resonance spectroscopy to monitor prostate response to therapy.

Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients’ outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: 2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT. 2012 Elsevier In

A method for the automatic reconstruction of fetal cardiac signals from magnetocardiographic recordings

Fetal magnetocardiography (fMCG) allows monitoring the fetal heart function through algorithms able to retrieve the fetal cardiac signal, but no standardized automatic model has become available so far. In this paper, we describe an automatic method that restores the fetal cardiac trace from fMCG recordings by means of a weighted summation of fetal components separated with independent component analysis (ICA) and identified through dedicated algorithms that analyse the frequency content and temporal structure of each source signal. Multichannel fMCG datasets of 66 healthy and 4 arrhythmic fetuses were used to validate the automatic method with respect to a classical procedure requiring the manual classification of fetal components by an expert investigator. ICA was run with input clusters of different dimensions to simulate various MCG systems. Detection rates, true negative and false positive component categorization, QRS amplitude, standard deviation and signal-to-noise ratio of reconstructed fetal signals, and real and per cent QRS differences between paired fetal traces retrieved automatically and manually were calculated to quantify the performances of the automatic method. Its robustness and reliability, particularly evident with the use of large input clusters, might increase the diagnostic role of fMCG during the prenatal period.status: publishe

Performance comparison of independent component analysis algorithms for fetal cardiac signal reconstruction: a study on synthetic fMCG data

Independent component analysis (ICA) algorithms have been successfully used for signal extraction tasks in the field of biomedical signal processing. We studied the performances of six algorithms (FastICA, CubICA, JADE, Infomax, TDSEP and MRMI-SIG) for fetal magnetocardiography (fMCG). Synthetic datasets were used to check the quality of the separated components against the original traces. Real fMCG recordings were simulated with linear combinations of typical fMCG source signals: maternal and fetal cardiac activity, ambient noise, maternal respiration, sensor spikes and thermal noise. Clusters of different dimensions (19, 36 and 55 sensors) were prepared to represent different MCG systems. Two types of signal-to-interference ratios (SIR) were measured. The first involves averaging over all estimated components and the second is based solely on the fetal trace. The computation time to reach a minimum of 20 dB SIR was measured for all six algorithms. No significant dependency on gestational age or cluster dimension was observed. Infomax performed poorly when a sub-Gaussian source was included; TDSEP and MRMI-SIG were sensitive to additive noise, whereas FastICA, CubICA and JADE showed the best performances. Of all six methods considered, FastICA had the best overall performance in terms of both separation quality and computation times.status: publishe

Fetal magnetocardiographic mapping using independent component analysis

Fetal magnetocardiography (fMCG) is the only noninvasive technique allowing effective assessment of fetal cardiac electrical activity during the prenatal period. The reconstruction of reliable magnetic field mapping associated with fetal heart activity would allow three-dimensional source localization. The efficiency of independent component analysis (ICA) in restoring reliable fetal traces from multichannel fMCG has already been demonstrated. In this paper, we describe a method of reconstructing a complete set of fetal signals hidden in multichannel fMCG preserving their correct spatial distribution, waveform, polarity and amplitude. Fetal independent components, retrieved with an ICA algorithm (FastICA), were interpolated (fICI method) using information gathered during FastICA iterations. The restored fetal signals were used to reconstruct accurate magnetic mapping for every millisecond during the average beat. The procedure was validated on fMCG recorded from the 22nd gestational week onward with a multichannel MCG system working in a shielded room. The interpolated traces were compared with those obtained with a standard technique, and the consistency of fetal mapping was checked evaluating source localizations relative to fetal echocardiographic information. Good magnetic field distributions during the P-QRS-T waves were attained with fICI for all gestational periods; their reliability was confirmed by three-dimensional source localizations.status: publishe

Optimal filter design for shielded and unshielded ambient noise reduction in fetal magnetocardiography

The greatest impediment to extracting high-quality fetal signals from fetal magnetocardiography (fMCG) is environmental magnetic noise, which may have peak-to-peak intensity comparable to fetal QRS amplitude. Being an unstructured Gaussian signal with large disturbances at specific frequencies, ambient field noise can be reduced with hardware-based approaches and/or with software algorithms that digitally filter magnetocardiographic recordings. At present, no systematic evaluation of filters' performances on shielded and unshielded fMCG is available. We designed high-pass and low-pass Chebychev II-type filters with zero-phase and stable impulse response; the most commonly used band-pass filters were implemented combining high-pass and low-pass filters. The achieved ambient noise reduction in shielded and unshielded recordings was quantified, and the corresponding signal-to-noise ratio (SNR) and signal-to-distortion ratio (SDR) of the retrieved fetal signals was evaluated. The study regarded 66 fMCG datasets at different gestational ages (22-37 weeks). Since the spectral structures of shielded and unshielded magnetic noise were very similar, we concluded that the same filter setting might be applied to both conditions. Band-pass filters (1.0-100 Hz) and (2.0-100 Hz) provided the best combinations of fetal signal detection rates, SNR and SDR; however, the former should be preferred in the case of arrhythmic fetuses, which might present spectral components below 2 Hz.status: publishe

Simultaneous monitoring of separate fetal magnetocardiographic signals in twin pregnancy

Fetal magnetocardiography (fMCG) allows the non-invasive recording of fetal cardiac electrical activity with increasing efficacy as gestation progresses. Many reports on the successful extraction of reliable fetal magnetocardiographic traces in singleton pregnancies exist in the literature, whereas there is only one report on the reconstruction of averaged fetal cardiac signals obtained in a twin pregnancy with the use of a double sensor array system. In this paper, we aimed at assessing the effectiveness of an ICA-based procedure to reconstruct the time course of fetal cardiac signals recorded with a single-shot multi-channel fMCG device in an uncomplicated twin pregnancy at 27 weeks. The evaluation of heart rate and beats synchronicity permitted the differentiation of fetal components; the quality of reconstructed fetal signals allowed visual inspection on single cycles and the simultaneous monitoring of separate fetal heart rate patterns. The proposed technique might be applied in twin pregnancies not only to characterize fetal arrhythmias, but also in all cases of discordant fetal growth, either in the case of intra-uterine growth retardation affecting one fetus, or in the case of twin-twin transfusion syndrome, a life-threatening condition where both fetuses are at risk of heart failure.status: publishe

GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity

The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in social behavior. The amygdala and mPFC are bidirectionally connected, functionally and anatomically, via the uncinate fasciculus. Recent evidence suggests that GABA-ergic neurotransmission within the mPFC could be central to the regulation of amygdala activity related to emotions and anxiety processing. However, the functional and neurochemical interactions within amygdala-mPFC circuits are unclear. In the current study, multimodal magnetic resonance imaging techniques were combined to investigate effective connectivity within the amygdala-mPFC network and its relationship with mPFC neurotransmission in 22 healthy subjects aged between 41 and 88 years. Effective connectivity in the amygdala-mPFC circuit was assessed on resting-state functional magnetic resonance imaging data using spectral dynamic causal modelling. State and trait anxiety were also assessed. The mPFC was shown to be the target of incoming outputs from the amygdalae and the source of exciting inputs to the limbic system. The amygdalae were reciprocally connected by excitatory projections. About half of the variance relating to the strength of top-down endogenous connection between right amygdala and mPFC was explained by mPFC GABA levels. State anxiety was correlated with the strength of the endogenous connections between right amygdala and mPFC. We suggest that mPFC GABA content predicts variability in the effective connectivity within the mPFC-amygdala circuit, providing new insights on emotional physiology and the underlying functional and neurochemical interactions.status: publishe

Beat-to-beat estimate of fetal cardiac time intervals using magnetocardiography: longitudinal charts of normality ranges and individual trends

BACKGROUND: Fetal magnetocardiography (fMCG) records fetal cardiac electro-physiological activity during the second half of gestation. We aimed at assessing normality values, related variability, and trends of fetal cardiac time intervals (fCTI) evaluated longitudinally from beat-to-beat fMCG analysis in uncomplicated pregnancies. MATERIALS AND METHODS: The fMCG were recorded with multi-channel system in shielded room. FCTI were estimated on more than 2600 fetal cardiac cycles from 51 fMCG data sets of uncomplicated pregnancies. Independent component analysis (ICA) allowed reconstructing reliable fetal signals for beat-to-beat identification of fCTI (RR, P wave, PQ, PR, QT, QTc, QRS, ST, and T wave); intra-individual variability analysis and trends were calculated; reference longitudinal charts accounted for intra- and inter-individual variations and were compared with figures estimated on averaged signals. RESULTS: For each data set, fCTI were calculated beat-to-beat on rhythm strips of more than 50 beats (95% overall detection rate). FCTI values, variability, and trends were in good agreement with available reference figures; intervals related to P and T waves were, respectively, underestimated and overestimated with respect to those estimated on averaged signals or obtained by other research groups. Errors were reduced and individual trends could be drawn. CONCLUSIONS: ICA permitted the reconstruction of reliable time course of fetal cardiac signals and the beat-to-beat calculation of time intervals, and normality ranges, with smaller errors with respect to previous studies. The retrieval of fetal traces with clear morphology and the longitudinal character of the study allowed estimating individual trends and beat-to-beat characterization, impossible with cross-sectional studies on averaged beats.status: publishe