EDITORIAL article Front. Neurosci., 24 April 2023Sec. Brain Imaging Methods Volume 17 - 2023 | https://doi.org/10.3389/fnins.2023.1200867

Introduction There is evidence that brain plasticity is the central mechanism involved in the functional recovery process of patients with knee osteoarthritis. Studies involving the analysis of central nervous system mechanisms of pain control and recovery could provide more data on future therapeutic approaches. Objective The aim of the study was to explore possible functional changes in cortical activity of patients submitted to knee osteoarthritis standardized pain treatment using electroencephalography. Methodology Ten patients with clinical and radiological diagnosis of painful knee unilateral or bilateral osteoarthritis were recruited to participate in clinical (Pain’s Visual Analog Scale), radiological (Kellgren-Lawrence Scale), and neurophysiological (electroencephalography) assessments to evaluate cortical activity during cortical pain modulation activity. The clinical and neurophysiological analyses were performed before and after standardized pain treatment. Results Eight patients participated in this study. A significant improvement in pain perception and relative increase in interhemispheric connectivity after therapies was observed. In electroencephalography analysis, tests with real movement showed a relative increase in density directed at Graph’s analysis. Conclusions Relative increase density directed measures at connectivity analysis in electroencephalography after pain treatment can be possible parameters to be explored in future research with a larger number of patients.

Here we dispel the lingering myth that Partial Directed Coherence is a Vector Autoregressive (VAR) Modelling dependent concept. In fact, our examples show that it is spectral factorization that lies at its heart, for which VAR modelling is a mere, albeit very efficient and convenient, device. This applies to Granger Causality estimation procedures in general and also includes instantaneous Granger effects. Care, however, must be exercised for connectivity between multivariate data generated through nonminimum phase mechanisms as it may possibly be incorrectly captured.

Here while we reminisce about how partial directed coherence was proposed, its motivation and evolution, we take the opportunity to relate it to some of its kin quantities and some of its offspring. Emphasis is placed on our development of asymptotic criteria to place it as a reliable investigation tool, where the connectivity detection problem is completely solved as opposed to what we call the characterization problem. We end by musing over some points now on our wishlist.

Using directed transfer function (DTF) and partial directed coherence (PDC) in the information version, this paper extends the theoretical framework to incorporate the instantaneous Granger causality (iGC) frequency domain description into a single unified perspective. We show that standard vector autoregressive models allow portraying iGC's repercussions associated with Granger connectivity, where interactions mediated without delay between time series can be easily detected.

e13553 Background: Mammography interpretation presents some challenges however, better technological approaches have allowed increased accuracy in cancer diagnosis and nowadays, radiologists sensitivity and specificity for mammography screening vary from 84.5 to 90.6 and 89.7 to 92.0%, respectively. Since its introduction in breast image analysis, artificial intelligence (AI) has rapidly improved and deep learning methods are gaining relevance as a companion tool to radiologists. Thus, the aim of this systematic review and meta analysis was to evaluate the sensitivity and specificity of AI deep learning algorithms and radiologists for breast cancer detection through mammography. Methods: A systematic review was performed using PubMed and the words: deep learning or convolutional neural network and mammography or mammogram, from January 2015 to October 2020. All titles and abstracts were doubly checked; duplicate studies and studies in languages other than English were excluded. The remaining complete studies were doubly assessed and those with specificity and sensibility information had data collected. For the meta analysis, studies reporting specificity, sensitivity and confidence intervals were selected. Heterogeneity measures were calculated using Cochran Q test (chi-square test) and the I2 (percentage of variation). Sensitivity and specificity and 95% confidence intervals (CI) values were calculated, using Stata/MP 14.0 for Windows. Results: Among 223 studies, 66 were selected for full paper analysis and 24 were selected for data extraction. Subsequently, only papers evaluating sensitivity, especificity, CI and/or AUC were analyzed. Eleven studies compared AUC using AI with another method and for these studies, a differential AUC was calculated, however no differences were observed: AI vs Reader (n = 3; p = 0.109); AI vs AI (n = 5; p = 0.225); AI vs AI + reader (n = 2; p = 0.180); AI + Reader vs reader (n = 2; p = 0.655); AI vs reader (n > 1) (n = 3; p = 0.102). Some studies had more than one comparison. A meta analysis was performed to evaluate sensitivity and specificity of the methods. Five studies were included in this analysis and a great heterogeneity among them was observed. There were studies evaluating more than one AI algorithm and studies comparing AI with readers alone or in combination with AI. Sensitivity for AI; AI + reader; reader alone, were 76.08; 84.02; 80.91, respectively. Specificity for AI; AI + reader; reader alone, were 96.62; 85.67; 84.89, respectively. Results are shown in the table. Conclusions: Although recent improvements in AI algorithms for breast cancer screening, a delta AUC between comparisons of AI algorithms and readers was not observed.[Table: see text]

Background: Pitch pattern sequence (PPS) and duration pattern sequence (DPS) tests are frequently used in the assessment of auditory processing disorder. Current recommendations suggest alternate, interchangeable modes for responding to stimuli. Purpose: The objective of the study is to evaluate the influence of response mode (i.e., humming, pointing, and labeling) and age on PPS and DPS performance of 7- to 11-year-old children. Research Design: Laboratory-based testing of school children. Cross-sectional comparison of age, with repeated measures of age, test, ear, and response mode. Study Sample: From 452 children recruited, 228 right-handed children (109 girls) aged 7 years to 11 years 11 months (mean age 9 years 4 months) completed at least one test (PPS: 211, DPS: 198), and 181 children completed both tests. Audiology inclusion criteria include normal hearing thresholds (<= 15 dB HL at octave frequencies 250-8000 Hz); word recognition in quiet >= 92%; tympanogram peak compensated static acoustic compliance 0.4-1.6 mmhos; and tympanometric peak pressure -100 to + 50 daPa, all in both ears. Other inclusion criteria were Portuguese as first language; right handed; no musical training; no related, known, or observed phonological, learning, neurologic, psychiatric, or behavioral disorder; otologic history; and delayed neuropsychomotor or language development. Data Collection and Analysis: PPS: 30 trials per ear and response condition of three consecutive 500 msec duration intermixed high (1430 Hz) or low (880 Hz) frequency tones presented monaurally at 50 dB HL. The first response condition was humming followed by labeling (naming: high or low). DPS: As per PPS except 1000 Hz tones of intermixed 500 (long) and 250 msec (short) duration. First response was pointing (at a symbolic object) followed by labeling. Trends across age and between tests were assessed using repeated measures generalized linear mixed models. Correlation coefficients were calculated to assess relations among test scores. The two-sided significance level was 0.05. Results: Older children performed better than younger children in all tasks. Humming the tone pattern (PPS humming) produced generally better performance than either articulating the attributes of the tones (labeling) or pointing to objects representing tone duration. PPS humming produced ceiling performance for many children of all ages. For both labeling tasks and DPS pointing, performance was better on the PPS than on the DPS, for stimulation of the right than the left ear, and in boys than girls. Individual performance on the two tasks was highly correlated. Conclusions: Response mode does matter in the PPS and DPS. Results from humming should not be combined with or be a substitute for results obtained from a labeling response. Tasks that rely on labeling a tonal stimulus should be avoided in testing hearing in children or other special populations.

The current study investigated the effect of conscious intention to act on the Bereitschaftspotential. Situations in which the awareness of acting is minimally expressed were generated by asking 16 participants to press a button after performing a mental imagery task based on animal pictures (automatic condition). The affective responses induced by the pictures were controlled by selecting the animals according to different valences, threatening and neutral. The Bereitschaftspotential associated with the button presses was compared to the observed when similar movements were performed under the basic instructions of the self-paced movement paradigm (willed condition). Enhanced Bereitschaftspotential amplitudes were observed in the willed condition with respect to the automatic condition. This effect was manifested as a negative slope at medial frontocentral sites during the last 500 ms before movement onset. The valence of the pictures did not affect the motor preparatory potentials. The results suggest that significant part of the NS’ subcomponent of the readiness potential is associated with the attention to—and, presumably, awareness of—intention to move, possibly reflecting cortical activation from supplementary motor areas. Secondarily, our findings supports that the feeling of threat does not influence the Bereitschaftspotential associated with automatic movements. Regarding methodological issues, the behavioural model of spontaneous voluntary movements proposed in automatic condition can benefit investigations on purely motor (or non-cognitive) subcomponents of the Bereitschaftspotential.

Objective: To present a unified mathematical derivation of the frequency-dependent asymptotic behavior of the three main forms of directed transfer function (DTF). Methods: A synthesis of the results (proved in an extended Appendix) is followed by a series of Monte Carlo simulations of representative examples. Results: DTF estimators are asymptotically normal when the true values are different from zero. Under the null hypothesis H 0 : DTF=0, the estimator is distributed as a linear combination of independent X 1 2 variables. Conclusions: Null DTF rejection is shown to be achievable with identical performance irrespective of which DTF form is adopted. Significance: Together with recent allied partial directed coherence results, this paper rounds up connectivity inference tools for a class of frequency-domain connectivity estimators.

As opposed to focal epilepsy, absence seizures do not exhibit a clear seizure onset zone or focus since its ictal activity rapidly engages both brain hemispheres. Yet recent graph theoretical analysis applied to absence seizures EEG suggests the cortical focal presence, an unexpected feature for this type of epilepsy. In this study, we explore the characteristics of absence seizure by classifying the nodes as to their source/sink natures via weighted directed graph analysis based on connectivity direction and strength estimation using information partial directed coherence (iPDC). By segmenting the EEG signals into relatively short 5-sec-long time windows we studied the evolution of coupling strengths from both sink and source nodes, and the network dynamics of absence seizures in eight patients.

In this article, we extend the statistical detection performance evaluation of linear connectivity from Sameshima et al. (in: Slezak et al. (eds.) Lecture Notes in Computer Science, 2014) via brand new Monte Carlo simulations of three widely used toy models under different data record lengths for a classic time domain multivariate Granger causality test, information partial directed coherence, information directed transfer function, and include conditional multivariate Granger causality whose behaviour was found to be anomalous.

In this work we show the asymptotic behavior of information partial directed coherence estimator via the Monte Carlo simulation of a particular toy model taken from the literature. We show that the control of false positive rate tends to the chosen significance level if detection decision is made at specific frequency values.

We present a unified mathematical derivation of the asymptotic behaviour of three of the main forms of \textit{directed transfer function} (DTF) complementing recent partial directed coherence (PDC) results \cite{Baccala2013}. Based on these results and numerical examples we argue for a new directed `link' centered neural connectivity framework to replace the widespread correlation based effective/functional network concepts so that directed network influences between structures become classified as to whether links are \textit{active} in a \textit{direct} or in an \textit{indirect} way thereby leading to the new notions of \textit{Granger connectivity} and \textit{Granger influenciability} which are more descriptive than speaking of Granger causality alone.

High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a "functional inhibition" of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation "local inhibition" and "distant excitation" is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS.

Sleep is beneficial to learning, but the underlying mechanisms remain controversial. The synaptic homeostasis hypothesis (SHY) proposes that the cognitive function of sleep is related to a generalized rescaling of synaptic weights to intermediate levels, due to a passive downregulation of plasticity mechanisms. A competing hypothesis proposes that the active upscaling and downscaling of synaptic weights during sleep embosses memories in circuits respectively activated or deactivated during prior waking experience, leading to memory changes beyond rescaling. Both theories have empirical support but the experimental designs underlying the conflicting studies are not congruent, therefore a consensus is yet to be reached. To advance this issue, we used real-time PCR and electrophysiological recordings to assess gene expression related to synaptic plasticity in the hippocampus and primary somatosensory cortex of rats exposed to novel objects, then kept awake (WK) for 60 min and finally killed after a 30 min period rich in WK, slow-wave sleep (SWS) or rapid-eye-movement sleep (REM). Animals similarly treated but not exposed to novel objects were used as controls. We found that the mRNA levels of Arc, Egr1, Fos, Ppp2ca and Ppp2r2d were significantly increased in the hippocampus of exposed animals allowed to enter REM, in comparison with control animals. Experience-dependent changes during sleep were not significant in the hippocampus for Bdnf, Camk4, Creb1, and Nr4a1, and no differences were detected between exposed and control SWS groups for any of the genes tested. No significant changes in gene expression were detected in the primary somatosensory cortex during sleep, in contrast with previous studies using longer post-stimulation intervals (>180 min). The experience-dependent induction of multiple plasticity-related genes in the hippocampus during early REM adds experimental support to the synaptic embossing theory.

High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a “functional inhibition” of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation “local inhibition” and “distant excitation” is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS.

After briefly recapping and reframing the problem of neural connectivity and its implications for today's brain mapping efforts, we argue that supplementing/replacing traditional conservative correlation based analysis methods requires active user understanding of the aims and limitations of the newly proposed multivariate analysis frameworks before the new methods can gain general acceptance and full profit can be made from the expanded descriptive opportunities they offer.

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.