Auditory cortical and hippocampal local-field potentials to frequency deviant tones in urethane-anesthetized rats: An unexpected role of the sound frequencies themselves

The human brain can automatically detect auditory changes, as indexed by the mismatch negativity of event-related potentials. The mechanisms that underlie this response are poorly understood. We recorded primary auditory cortical and hippocampal (dentate gyrus, CA1) local-field potentials to serial tones in urethane-anesthetized rats. In an oddball condition, a rare (deviant) tone (p = 0.11) randomly replaced a repeated (standard) tone. The deviant tone was either lower (2200, 2700, 3200, 3700 Hz) or higher (4300, 4800, 5300, 5800 Hz) in frequency than the standard tone (4000 Hz). In an equiprobability control condition, all nine tones were presented at random (p = 0.11). Differential responses to deviant tones relative to the standard tone were found in the auditory cortex and the dentate gyrus but not in CA1. Only in the dentate gyrus, the responses were found to be standard- (i.e., oddball condition-) specific. In the auditory cortex, the sound frequencies themselves sufficed to explain their generation. These findings tentatively suggest dissociation among non-contextual afferent, contextual afferent and auditory change detection processes. Most importantly, they remind us about the importance of strict control of physical sound features in mismatch negativity studies in animals.     

Commonalities and differences in the spatiotemporal neural dynamics associated with automatic attentional shifts induced by gaze and arrows

Gaze and arrows automatically trigger attentional shifts. Neuroimaging studies have identified a commonality in the spatial distribution of the neural activation involved in such attentional shifts. However, it remains unknown whether these activations occur with common temporal profiles. To investigate this issue, magnetoencephalography (MEG) was used to evaluate neural activation involved in attentional shifts induced by gaze and arrows. MEG source reconstruction analyses revealed that the superior temporal sulcus and the inferior frontal gyrus were commonly activated after 200 ms, in response to directional versus non-directional cues. Regression analyses further revealed that the magnitude of brain activity in these areas and in the bilateral occipital cortex was positively related to the effect of attentional shift on reaction times under both the gaze and the arrow conditions. The results also revealed that some brain regions were activated specifically in response to directional versus non-directional gaze or arrow cues at the 350–400 ms time window. These results suggest that the neural mechanisms underlying attentional shifts induced by gaze and arrows share commonalities in their spatial distributions and temporal profiles, with some spatial differences at later time stages.     

Steady state visually evoked potential (SSVEP) topography changes associated with cocoa flavanol consumption

In a randomized, double-blind placebo controlled trial, 63 middle-aged volunteers aged between 40 and 65 years were administered a daily chocolate drink containing 250 mg or 500 mg cocoa flavanols versus a low cocoa flavanol (placebo) drink over a 30-day period. Participants were tested at baseline as well as at the end of the treatment period on a test of Spatial Working Memory. Steady State Probe Topography (SST) was used to assess neurocognitive changes associated with cocoa flavanol supplementation during the completion of the Spatial Working Memory task. SST is an electrophysiological technique which utilizes a 13 Hz diffuse visual flicker in order to generate a steady state visually evoked potential (SSVEP). Changes in the amplitude and phase of the SSVEP response after 30 days were compared between treatment groups. Behavioral measures of accuracy and reaction time were not found to be significantly different between treatment groups, while average SSVEP amplitude and phase differences at a number of posterior parietal and centro-frontal sites were found to be significantly different between groups during memory encoding, the working memory hold period and retrieval. In the absence of significant behavioral effects, these differences in brain activation can be interpreted as evidence of increased neural efficiency in spatial working memory function associated with chronic cocoa flavanol consumption.     

Estimation of pulse transit time using two diametric blood pressure waveform measurements

This paper presents a novel method to estimate the aortic-to-peripheral pulse transit time (PTT) using the blood pressure waveforms measured at two diametric peripheral locations, for instance, one on an upper extremity and the other on a lower extremity. The method is based on a computational relationship between the two peripheral blood pressures, which is derived by first relating each peripheral blood pressure to a common central aortic blood pressure. The parameters of the computational relationship for an individual subject can be identified by fitting them to two peripheral blood pressure waveform measurements, thereby characterizing the cardiovascular dynamics, from which absolute changes in the PTT between the central aorta and each peripheral measurement site can be determined. The strength of the method is that it does not require any a priori knowledge of the peripheral measurement locations nor of the physiologic condition of the cardiovascular system. Experimental results are provided from five healthy swine subjects whose actual PTT experimentally varied from 44.9 ms to 163.0 ms (76.7 ms mean ± 26.4 ms SD). Compared to the reference PTT measurement, the novel method proposed in this paper estimated PTT within 3.7 ms mean ± 4.2 ms SD after initial calibration.     

Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex

Electrical stimulation of the primary visual cortex (V1) is an experimental approach for visual prostheses. We here compared the response to intracortical and epicortical stimulation of the primary visual cortex by using c-Fos immunoreactivity as a marker for neuronal activation.The primary visual cortex of male Sprague Dawley rats was unilaterally stimulated for four hours using bipolar electrodes placed either intracortically in layer IV (n = 26) or epicortically (n = 20). Four different current intensities with a constant pulse width of 200 μs and a constant frequency of 10 Hz were used, for intracortical stimulation with an intensity of 0 μA (sham-stimulation), 10 μA, 20 μA and 40 μA, and for epicortical stimulation 0 μA, 400 μA, 600 μA and 800 μA. Subsequently all animals underwent c-Fos immunostaining and c-Fos expression was assessed in layer I–VI of the primary visual cortex within 200 μm and 400 μm distance to the stimulation site. C-Fos expression was higher after intracortical stimulation compared to epicortical stimulation, even though ten times lower current intensities were applied. Furthermore intracortical stimulation resulted in more focal neuronal activation than epicortical stimulation. C-Fos expression was highest after intracortical stimulation with 20 μA compared to all other intensities. Epicortical stimulation showed a linear increase of c-Fos expression with the highest expression at 800 μA. Sham stimulation showed similar expression of c-Fos in both hemispheres. The contralateral hemisphere was not affected by intracortical or epicortical stimulation of either intensities. In summary, intracortical stimulation resulted in more focal neuronal activation with less current than epicortical stimulation. This model may be used as a simple but reliable model to evaluate electrodes for microstimulation of the primary visual cortex before testing in more complex settings.     

A robust wavelet-based multi-lead electrocardiogram delineation algorithm

A robust multi-lead ECG wave detection-delineation algorithm is developed in this study on the basis of discrete wavelet transform (DWT). By applying a new simple approach to a selected scale obtained from DWT, this method is capable of detecting QRS complex, P-wave and T-wave as well as determining parameters such as start time, end time, and wave sign (upward or downward). First, a window with a specific length is slid sample to sample on the selected scale and the curve length in each window is multiplied by the area under the absolute value of the curve. In the next step, a variable thresholding criterion is designed for the resulted signal. The presented algorithm is applied to various databases including MIT-BIH arrhythmia database, European ST-T Database, QT Database, CinC Challenge 2008 Database as well as high resolution Holter data of DAY Hospital. As a result, the average values of sensitivity and positive predictivity Se = 99.84% and P+ = 99.80% were obtained for the detection of QRS complexes, with the average maximum delineation error of 13.7 ms, 11.3 ms and 14.0 ms for P-wave, QRS complex and T-wave, respectively. The presented algorithm has considerable capability in cases of low signal-to-noise ratio, high baseline wander, and abnormal morphologies. Especially, the high capability of the algorithm in the detection of the critical points of the ECG signal, i.e. the beginning and end of T-wave and the end of the QRS complex was validated by cardiologists in DAY hospital and the maximum values of 16.4 ms and 15.9 ms were achieved as absolute offset error of localization, respectively.     

The impact of environmental metals in young urbanites’ brains

Air pollution exposures are linked to cognitive and olfaction deficits, oxidative stress, neuroinflammation and neurodegeneration including frontal hyperphosphorylated tau and diffuse amyloid plaques in Mexico City children and young adults. Mexico City residents are chronically exposed to fine particulate matter (PM_2.5) concentrations (containing toxic combustion and industrial metals) above the annual standard (15 μg/m³) and to contaminated water and soil. Here, we sought to address the brain-region-specific effects of metals and key neuroinflammatory and DNA repair responses in two air pollution targets: frontal lobe and olfactory bulb from 12 controls vs. 47 Mexico City children and young adults average age 33.06 ± 4.8 SE years. Inductively coupled plasma mass spectrometry (metal analysis) and real time PCR (for COX2, IL1β and DNA repair genes) in target tissues. Mexico City residents had higher concentrations of metals associated with PM: manganese (p = 0.003), nickel and chromium (p = 0.02) along with higher frontal COX2 mRNA (p = 0.008) and IL1β (p = 0.0002) and COX2 (p = 0.005) olfactory bulb indicating neuroinflammation. Frontal metals correlated with olfactory bulb DNA repair genes and with frontal and hippocampal inflammatory genes. Frontal manganese, cobalt and selenium increased with age in exposed subjects.Together, these findings suggest PM–metal neurotoxicity causes brain damage in young urbanites, the olfactory bulb is a target of air pollution and participates in the neuroinflammatory response and since metal concentrations vary significantly in Mexico City urban sub-areas, place of residency has to be integrated with the risk for CNS detrimental effects particularly in children.     

Early emotion discrimination in 8- to 10-year-old children: Magnetoencephalographic correlates

Emotional cues motivate attention and modulate event-related potentials as well as magnetic fields in adults. Central components enhanced by emotional content are Early Posterior Negativity (EPN, 150–300 ms) and Late Positive Potential (LPP, >300 ms). Previous electroencephalography studies in children revealed a differentiation of the late component in response to emotional scenes, but failed to detect an EPN effect. Twenty-two children aged 8–10 years saw 200 arousing pleasant and non-arousing neutral pictures in a rapid serial visual presentation (RSVP) design, while event-related magnetic fields were recorded with whole-head magnetoencephalography (MEG). Analysis of MEG data based on individual picture ratings yielded LPP-m but also EPN-m effects with topography and latency resembling that of adults. Thus, the mechanism of motivated attention at early processing stages (>150 ms) appears mature in children of this age group.     

Regionally-specific changes in levels of tumour necrosis factor in the dorsolateral prefrontal cortex obtained postmortem from subjects with major depressive disorder

BackgroundFrom studies in the periphery, changed levels of tumour necrosis factor (TNF) have been implicated in the pathophysiology of major depressive disorders (MDD). Therefore we decided to determine whether TNF was altered in the frontal cortex (Brodmann's areas (BA) 24 and 46) from 10 subjects with MDD and 10 control subjects.MethodsTissue homogenates were prepared from the left hemisphere and levels of TNF trans-membrane (tmTNF) and TNF soluble (sTNF) forms measured by Western blots.ResultstmTNF was significantly increased in BA 46 (mean ± SEM: 7.70 ± 0.92 vs. 3.18 ± 0.87 Ratio Internal Control, p < 0.001), but not BA 24, from subjects with MDD, there was no change in levels of sTNF in either CNS region.LimitationsAs the report of tmTNF in postmortem CNS from subjects with MDD, our findings need to be replicated in another group of cases.ConclusionsOur data supports the hypothesis that changes in pro-inflammatory pathways may be involved in the pathophysiology of MDD. Targeting these pathways may be a new approach to treating the disorder.     

Reading words and pseudowords in dyslexia: ERP and behavioural tests in English-speaking adolescents

The study reports neurophysiological and behavioural correlates of lexical decision processes in English speaking dyslexic and non-dyslexic readers. Nine dyslexic adolescents (ages 15.6–17.8) and 9 control (ages 15.4–19.3) adolescents were tested, and the event related potentials (ERPs) to words and pseudowords were recorded simultaneously with behavioural measures. As expected, both groups showed significantly lower accuracy and longer response times for the pseudowords. Furthermore, overall performance (in terms of lower accuracy and longer response times) was significantly worse for the dyslexic group. The ERP analysis indicated that the later positive peaks, P4 (around 400 ms from stimulus onset) and P5 (around 500 ms), were significantly delayed and attenuated for the dyslexic group. Analysis of the early ERP peaks recorded in the occipitotemporal region led to an interesting dissociation. The controls showed a left lateralised Condition effect, with the amplitude of P1 significantly smaller to words than pseudowords. By contrast, there was no such lexical effect for the dyslexic group, with equal P1 amplitudes for words and pseudowords, at the control level for pseudowords. The deviations in the early ERP components of dyslexics support the evidence of deficits in pre-lexical visual word form recognition within the first 110 ms of activation together with altered hemispheric asymmetry. In addition, the slowed and attenuated late ERP components and weaker behavioural performance of the dyslexic group highlight deficits in the later, cognitive, processing stages.     

Neural mechanisms of detecting and orienting attention toward unattended threatening somatosensory targets. I. Intermodal effects

Our previous work has identified four components of the somatosensory-evoked potential elicited by painful electrical stimulation of the sural nerve that might index an involuntary process that detects and orients attention toward threatening somatosensory stimuli. These components include a negativity over the central scalp at 70-110 ms poststimulus (CN70-110), a contralateral temporal negativity at 100-180 ms (CTN100-180), a frontocentral negativity at 130-200 ms, and a positive potential at 270-340 ms (the pain-related P2). The results of the endogenous cuing experiment used here suggest that the CN70-110 and CTN100-180 index somatosensory cortex activity that detects a threatening somatosensory stimulus when the subject's attention is focused on another stimulus modality but not another location. The P2, on the other hand, appears to index inferior parietal cortex activity that is specifically involved in orienting spatial attention.     

New approach for T-wave peak detection and T-wave end location in 12-lead paced ECG signals based on a mathematical model

This paper presents an innovative approach for T-wave peak detection and subsequent T-wave end location in 12-lead paced ECG signals based on a mathematical model of a skewed Gaussian function. Following the stage of QRS segmentation, we establish search windows using a number of the earliest intervals between each QRS offset and subsequent QRS onset. Then, we compute a template based on a Gaussian-function, modified by a mathematical procedure to insert asymmetry, which models the T-wave. Cross-correlation and an approach based on the computation of Trapezium's area are used to locate, respectively, the peak and end point of each T-wave throughout the whole raw ECG signal. For evaluating purposes, we used a database of high resolution 12-lead paced ECG signals, recorded from patients with ischaemic cardiomyopathy (ICM) in the University Hospitals of Leicester NHS Trust, UK, and the well-known QT database. The average T-wave detection rates, sensitivity and positive predictivity, were both equal to 99.12%, for the first database, and, respectively, equal to 99.32% and 99.47%, for QT database. The average time errors computed for T-wave peak and T-wave end locations were, respectively, ?0.38 ± 7.12 ms and ?3.70 ± 15.46 ms, for the first database, and 1.40 ± 8.99 ms and 2.83 ± 15.27 ms, for QT database. The results demonstrate the accuracy, consistency and robustness of the proposed method for a wide variety of T-wave morphologies studied.     

Maturational changes of 5 Hz SSVEPs elicited by intermittent photic stimulation

We investigated the development of the magnitude and phase alignment of steady-state visual evoked potentials induced by 5 Hz intermittent photic stimulation in 46 children (3 to 16 years) and 8 adults, as a function of age. We found that, over the occipital region, magnitude values were the highest in 8–11-year old children, but decreased with age over all other cerebral regions. Phase alignment values increased with age over the occipital, parietal and frontal cerebral regions. We interpret these findings in terms of the development of functional interactions between different cortical areas involved in the processing of visual stimuli.     

An event-related potential study on exposure therapy for patients suffering from spider phobia

The present event-related potential (ERP) study investigated electrocortical changes related to cognitive behavior therapy (CBT) in spider phobic females. Forty-five patients and twenty non-phobic women were presented with phobia-relevant, generally fear-inducing, disgust-inducing and affectively neutral pictures in a first EEG session. Phobic patients were randomly assigned to either a therapy (TG) or a waiting-list (WG) group. EEG measurement was repeated after CBT or a waiting period. ERPs were extracted in the time windows 340–500 ms (P300), 550–770 ms (late positive potential (LPP), early LPP) and 800–1500 ms (late LPP). Relative to controls, untreated phobics showed enhanced amplitudes of P300 and early LPP in response to spider pictures. This most likely reflects the emotional significance of the phobic stimulus, which automatically draws attention. The therapy effect consisted of a significant enhancement of late LPP amplitudes in response to spider pictures. Results are discussed in terms of reduced attentional avoidance.     

Hemifield-dependent N1 and event-related theta/delta oscillations: An unbiased comparison of surface Laplacian and common EEG reference choices

Surface Laplacian methodology has been used to reduce the impact of volume conduction and arbitrary choice of EEG recording reference for the analysis of surface potentials. However, the empirical implications of employing these different transformations to the same EEG data remain obscure. This study directly compared the statistical effects of four commonly-used (nose, linked mastoids, average) or recommended (reference electrode standardization technique [REST]) references and their spherical spline current source density (CSD) transformation for a large data set stemming from a well-understood experimental manipulation. ERPs (72 sites) recorded from 130 individuals during a visual half-field paradigm with highly-controlled emotional stimuli were characterized by mid-parietooccipital N1 (125 ms peak latency) and event-related synchronization (ERS) of theta/delta (160 ms), which were most robust over the contralateral hemisphere. All five data transformations were rescaled to the same covariance and submitted to a single temporal or time-frequency PCA (Varimax) to yield simplified estimates of N1 or theta/delta ERS. Unbiased nonparametric permutation tests revealed that these hemifield-dependent asymmetries were by far most focal and prominent for CSD data, despite all transformations showing maximum effects at mid-parietooccipital sites. Employing smaller subsamples (signal-to-noise) or window-based ERP/ERS amplitudes did not affect these comparisons. Furthermore, correlations between N1 and theta/delta ERS at these sites were strongest for CSD and weakest for nose-referenced data. Contrary to the common notion that the spatial high pass filter properties of a surface Laplacian reduce important contributions of neuronal generators to the EEG signal, the present findings demonstrate that instead volume conduction inherent in surface potentials weakens the representation of neuronal activation patterns at scalp that directly reflect regional brain activity.     

Fast purinergic transmission in the central nervous system

Fast synaptic transmission mediated by P_2XATP receptors is a recent discovery in the central nervous system and new information on the distribution of P_2Xbinding sites and mRNA for P_2Xreceptor subunits in the brain suggests that transmission mediated by ATP may be widespread. P_2XATP receptors have many functional similarities to other receptors mediating fast excitatory synaptic transmission and some significant differences. ATP release is calcium-dependent and vesicular in nature. Individual synaptic currents are small in size (around 10 pA at −70 mV), have a fast rise-time and decay with a time-course (decay tau = 18 ms at −70 mV) intermediate between that of AMPA receptor-mediated synaptic currents and NMDA receptor-mediated synaptic currents. It is likely that P_2XATP receptor channels are permeable to calcium suggesting by analogy with glutamatergic transmission that purinergic transmission will participate in the regulation of calcium-dependent processes in neurones.     

A human experimental model of episodic pain

An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants were subjected to 45 min of intense painful cutaneous electrical stimulation (episodic pain session), using a stimulus paradigm that in animals has been shown to induce long-term potentiation. These electrical stimulations produced a verbal pain rating of approximately 85 on a 0–100 verbal rating scale (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused significantly increased cutaneous blood flow around the site of the stimulation. Axon flare reflex and blood flow reached a plateau on day one in all the subjects and no significant changes between the days were observed. The results showed that the effect of the electrical stimulations changed over the five days; pain potentiation was induced on the first day (significant increase in the verbal pain ratings during the 45 min stimulation) but not on any of the subsequent days. After five days of subsequent pain induction, the global field power showed a significant reduction in P2 amplitude in the late stage (200–370 ms, in the central–parietal area). In conclusion, the results suggest that in healthy individuals this model of episodic pain produces a rapid adaptation after day one and that generates significant SEP changes at day five.     

Comparison between kinematic and ground reaction force techniques for determining gait events during treadmill walking at different walking speeds

This study involved a comparison of kinematics-based and ground reaction force (GRF)-based event detection methods. The objectives were (1) to assess the difference between the determination of gait events from GRF-based and kinematic/ultrasound-based techniques and (2) to determine the effects of gait speed on the agreement between the two techniques. At combined speeds, the average of the true difference was 2.6 ± 2.8 ms for heel strike and ?1.3 ± 2.4 ms for toe-off identification. A positive value indicated that GRF-based identification occurred before kinematics-based identification. The average of the true difference was ?3.9 ± 3.5 ms for the duration of stance; thus, the duration of stance as determined by the kinematics-based technique was shorter than that determined by GFR-based detection. Strong correlations (range 0.948–0.974) were found at all (slow, moderate, and fast) gait speeds. Near unity of slope of the linear regression line (range 0.955–1.008) was identified for the duration of stance between the two methods. Our results suggest that the agreement between the two event detection methods depended on gait speed, but the differences were small. The data determined using kinematic/ultrasound-based and GRF-based methods were comparable in healthy participants.     

Comparison of three methods for identifying the heelstrike transient during walking gait

Impulsive, or high rate, loading contributes to cartilage degradation and is commonly identified via the heelstrike transient (HST) in the vertical ground reaction force (vGRF) during gait. Investigation of the HST may improve our understanding of knee osteoarthritis mechanical pathogenesis. However, the most appropriate method for objectively identifying the HST is unclear. Twenty-eight healthy subjects walked at a self-selected pace while vGRF data were captured. The efficacies of three HST identification methods (Radin, Hunt, and Modified Hunt) were evaluated using vGRF data lowpass filtered at three frequencies (raw/unfiltered, 75 Hz, and 50 Hz). Both the HST identification method and lowpass filter frequency influenced whether a HST was identified and whether a subject was classified as an “impulsive loader” (i.e. HST identified in 3 of 5 trials). The methods identified different phenomena in the vGRF, with the Radin and Modified Hunt methods identifying the HST 11-16 ms following ground contact and the Hunt method identifying the HST 83–122 ms following ground contact. Lowpass filtering the vGRF at 75 Hz and implementing the Radin method was the most effective approach for identifying the HST. Future longitudinal observations are necessary to determine if specific HST criteria are indicative of knee osteoarthritis development and progression.