Partial directed coherence: twenty years on some history and an appraisal.

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.

Frequency Domain Repercussions of Instantaneous Granger Causality.

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.

The effect of conscious intention to act on the Bereitschaftspotential.

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.

Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

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.

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, ß = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, ß = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.

Experience-dependent upregulation of multiple plasticity factors in the hippocampus during early REM sleep.

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.

Partial Directed Coherence and the Vector Autoregressive Modelling Myth and a Caveat.

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.

Functional Changes in Cortical Activity of Patients Submitted to Knee Osteoarthritis Treatment: An Exploratory Pilot Study.

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.

Hyperdopaminergia and NMDA receptor hypofunction disrupt neural phase signaling.

Neural phase signaling has gained attention as a putative coding mechanism through which the brain binds the activity of neurons across distributed brain areas to generate thoughts, percepts, and behaviors. Neural phase signaling has been shown to play a role in various cognitive processes, and it has been suggested that altered phase signaling may play a role in mediating the cognitive deficits observed across neuropsychiatric illness. Here, we investigated neural phase signaling in two mouse models of cognitive dysfunction: mice with genetically induced hyperdopaminergia [dopamine transporter knock-out (DAT-KO) mice] and mice with genetically induced NMDA receptor hypofunction [NMDA receptor subunit-1 knockdown (NR1-KD) mice]. Cognitive function in these mice was assessed using a radial-arm maze task, and local field potentials were recorded from dorsal hippocampus and prefrontal cortex as DAT-KO mice, NR1-KD mice, and their littermate controls engaged in behavioral exploration. Our results demonstrate that both DAT-KO and NR1-KD mice display deficits in spatial cognitive performance. Moreover, we show that persistent hyperdopaminergia alters interstructural phase signaling, whereas NMDA receptor hypofunction alters interstructural and intrastructural phase signaling. These results demonstrate that dopamine and NMDA receptor dependent glutamate signaling play a critical role in coordinating neural phase signaling, and encourage further studies to investigate the role that deficits in phase signaling play in mediating cognitive dysfunction.

The sleep-wake cycle in adult rats following pilocarpine-induced temporal lobe epilepsy.

The relationship between sleep and epilepsy is both complex and clinically significant. Temporal lobe epilepsy (TLE) influences sleep architecture, while sleep plays an important role in facilitating and/or inhibiting possible epileptic seizures. The pilocarpine experimental model reproduces several features of human temporal lobe epilepsy and is one of the most widely used models in basic research. The aim of the present study was to characterize, behaviorally and electrophysiologically, the phases of sleep-wake cycles (SWC) in male rats with pilocarpine-induced epilepsy. Epileptic rats presented spikes in all phases of the SWC as well as atypical cortical synchronization during attentive wakefulness and paradoxical sleep. The architecture of the sleep-wake phases was altered in epileptic rats, as was the integrity of the SWC. Because our findings reproduce many relevant features observed in patients with epilepsy, this model is suitable to study sleep dysfunction in epilepsy.

Information theoretic interpretation of frequency domain connectivity measures.

In order to provide adequate multivariate measures of information flow between neural structures, modified expressions of partial directed coherence (PDC) and directed transfer function (DTF), two popular multivariate connectivity measures employed in neuroscience, are introduced and their formal relationship to mutual information rates are proved.

Frequency domain connectivity identification: an application of partial directed coherence in fMRI.

Functional magnetic resonance imaging (fMRI) has become an important tool in Neuroscience due to its noninvasive and high spatial resolution properties compared to other methods like PET or EEG. Characterization of the neural connectivity has been the aim of several cognitive researches, as the interactions among cortical areas lie at the heart of many brain dysfunctions and mental disorders. Several methods like correlation analysis, structural equation modeling, and dynamic causal models have been proposed to quantify connectivity strength. An important concept related to connectivity modeling is Granger causality, which is one of the most popular definitions for the measure of directional dependence between time series. In this article, we propose the application of the partial directed coherence (PDC) for the connectivity analysis of multisubject fMRI data using multivariate bootstrap. PDC is a frequency domain counterpart of Granger causality and has become a very prominent tool in EEG studies. The achieved frequency decomposition of connectivity is useful in separating interactions from neural modules from those originating in scanner noise, breath, and heart beating. Real fMRI dataset of six subjects executing a language processing protocol was used for the analysis of connectivity.

Pitch and Duration Pattern Sequence Tests in 7- to 11-Year-Old Children: Results Depend on Response Mode.

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.

Baseline hippocampal theta oscillation speeds correlate with rate of operant task acquisition.

Many lines of evidence indicate that theta rhythm, a prominent neural oscillatory mode found in the mammalian hippocampus, plays a key role in the acquisition, processing, and retrieval of memories. However, a predictive neurophysiological feature of the baseline theta rhythm that correlates with the learning rate across different animals has yet to be identified. Here we show that the mean theta rhythm speed observed during baseline periods of immobility has a strong positive correlation with the rate at which rats learn an operant task. This relationship is observed across rats, during both quiet waking (r=0.82; p<0.01) and paradoxical sleep (r=0.83; p<0.01), suggesting that the basal theta frequency relates to basic neurological processes that are important in the acquisition of operant behavior.

Temporal organization skills in cochlear implants recipients.

UNLABELLED: Processing acoustic clues from the sounds of speech depends on the proper perception of the frequency and duration of stimuli as a sequence of events. AIM: To assess the capacity for temporal organization in users of multichannel CI. METHOD: 14 normal hearing individuals formed the control group, matching in age and gender other 14 users of multichannel CI, who made up the study group, and they were assessed and compared as to the Frequency Patterns Test (FPT) and Duration Patterns Test (DPT). RESULTS: CI users had good performance in temporal organization tasks, with mean results of 48.7% in the FPT and 59.6% in the DPT. For the control group, mean performance at the FPT was of 63.4% and in the DPT of 64.6%. We did not see statistically significant difference between the results from the control and study groups. CONCLUSION: The CI provided favorable performance in the tasks that required temporal organization skill for individuals evaluated in this study.

VOCALIZATIONS AND ASSOCIATED BEHAVIORS OF THE SOMBRE HUMMINGBIRD (APHANTOCHROA CIRRHOCHLORIS) AND THE RUFOUS-BREASTED HERMIT (GLAUCIS HIRSUTUS).

Vocal behavior in tropical hummingbirds is a new area of study. Here, we present findings on the vocalizations and associated behaviors of two species: Sombre Hummingbird (Aphantochroa cirrhochloris) and Rufous-breasted Hermit (Glaucis hirsutus). These are the only hummingbirds in which the brain areas activated by singing have been demonstrated. They are also among the basal species of their respective subfamilies, Trochilinae and Phaethornithinae and, thus, represent early stages in the evolution of hummingbird vocal communication. We found that the two species exhibit distinctive vocalizations and behaviors. Sombre Hummingbird calls had more modulation and were often used during agonistic interactions, whereas Rufous-breasted Hermit calls had higher pitch and purer tones and were produced in less aggressive interactions. Sombre Hummingbird song was highly stereotyped in syllable structure and syntax, whereas Rufous-breasted Hermit song was highly variable. Comparative analysis points to consistent similarities in use of vocalizations by the Sombre Hummingbird and other trochilines, and by the Rufous-breasted Hermit and other phaethornithines. We hypothesize that differences in vocal behavior between hummingbird lineages arise as adaptations to their foraging strategies.

[Biologic artifacts in quantitative EEG]. / Artefatos biológicos no EEG quantitativo.

We studied the influence of five biologic artifacts sources on quantitative EEG (blinking, forced eyes closure, forced jaw closure, tongue movements and pursuit eyes movements) through both visual and spectral analysis, with the purpose of verifying how do these artifacts can be seen in a cartographic way. We found that the spectrums potentials showed the same topographic display that was found through visual analysis. Visual analysis was superior than the quantitative evaluation to recognise the artifacts, as the former preserved the morphological display of the paroxysms. However it is important know how do the potentials are represented in quantitative maps, so that they can be identified as artifacts and not as pathologic EEG activity.

Directed Transfer Function: Unified Asymptotic Theory and Some of Its Implications.

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 H0: DTF=0, the estimator is distributed as a linear combination of independent χ21 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.

Deep Brain Stimulation: More Complex than the Inhibition of Cells and Excitation of Fibers.

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.