Stimulus Protocols Research Articles

Acute Optogenetic Modulation of Cardiac Twitch Dynamics Explored Through Modeling.

Optogenetic approaches allow cellular membrane potentials to be perturbed by light. When applied to muscle cells, mechanical events can be controlled through a process that could be termed "optomechanics." Besides functioning as an optical on/off switch, we hypothesized that optomechanical control could include the ability to manipulate the strength and duration of contraction events. To explore this possibility, we constructed an electromechanical model of the human ventricular cardiomyocyte while adding a representation of channelrhodopsin-2 (ChR2), a light-activated channel commonly used in optogenetics. Two hybrid stimulus protocols were developed that combined light-based stimuli with traditional electrical current (all-or-none) excitation. The first protocol involved delivery of a subthreshold optical stimulus followed 50-90 ms later by an electrical stimulus. The result was a graded inhibition of peak cellular twitch force in concert with a prolongation of the intracellular Ca2+ transient. The second protocol was comprised of an electrical stimulus followed by a long light pulse (250-350 ms) that acted to prolong the cardiac action potential (AP). This created a pulse duration-dependent prolongation of the intracellular Ca2+ transient that in turn altered the rate of muscle relaxation without changing peak twitch force. These results illustrate the feasibility of acute, optomechanical manipulation of cardiomyocyte contraction and suggest that this approach could be used to probe the dynamic behavior of the cardiac sarcomere without altering its intrinsic properties. Other experimentally meaningful stimulus protocols could be designed by making use of the optomechanical cardiomyocyte model presented here.

Development of a cognitive training program for the elderly

Abstract Introduction: Plasticity in intellectual functioning has been the target of significant research investment. Among non-pharmacological interventions, cognitive training appears as a promising option for delaying the effects of aging on cognition. Objective: The present study describes the procedures of a cognitive training program for healthy Brazilian elderly persons (without diagnosis of dementia). Method: Cognitive tasks for the training of attention, processing speed, episodic memory and working memory were carried out. The program training was performed over 12 individual sessions, and included an Instruction Book, a Stimulus Book and Protocol Record. To assess the effects of training, five subtests of the WAIS-III test were used: Picture completion, Coding, Arithmetic, Matrix Reasoning and Digit Span. The cognitive training program was tested with 15 individuals, divided into an experimental group (EG), which received training, and a control group (CG). The EG was formed of seven participants, aged between 70 and 82 years (M=73.57, SD=4.11) and with an average schooling of 5.8 years (SD=1.02). The CG was formed by 8 participants, aged 69-77 years (M=74.00, SD=4.58), and who had an average schooling of 2.88 years (SD=2.58). Results: Repeated measures ANOVA revealed a training effect for three subtests: Coding: [F(1)=5.40, p=0.03, η2G=0.09], Arithmetic [F(1)=9.03, p=0.01, η2G=0.004] and Picture completion [F(1)=8.01, p=0.01, η2G=0.19]. There were no gain effects for Matrix Reasoning [F(1)=1.43, p=0.25] and Digit Span [F(1)=10.04, p<0.001]. Conclusion: The results of this pilot study show the importance of testing the impact of cognitive training through a randomized clinical trial to verify its effects on the mental performance of older adults. The importance of greater disclosure in literature of the construction procedures involved in cognitive training tasks, as well as the formulation of intervention strategies, is highlighted.

A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network.

Chemotaxis is a dynamic cellular process, comprised of direction sensing, polarization and locomotion, that leads to the directed movement of eukaryotic cells along extracellular gradients. As a primary step in the response of an individual cell to a spatial stimulus, direction sensing has attracted numerous theoretical treatments aimed at explaining experimental observations in a variety of cell types. Here we propose a new model of direction sensing based on experiments using Dictyostelium discoideum (Dicty). The model is built around a reaction-diffusion-translocation system that involves three main component processes: a signal detection step based on G-protein-coupled receptors (GPCR) for cyclic AMP (cAMP), a transduction step based on a heterotrimetic G protein Gα2βγ, and an activation step of a monomeric G-protein Ras. The model can predict the experimentally-observed response of cells treated with latrunculin A, which removes feedback from downstream processes, under a variety of stimulus protocols. We show that cycling modulated by Ric8, a nonreceptor guanine exchange factor for in Dicty, drives multiple phases of Ras activation and leads to direction sensing and signal amplification in cAMP gradients. The model predicts that both and Gβγ are essential for direction sensing, in that membrane-localized , the activated GTP-bearing form of , leads to asymmetrical recruitment of RasGEF and Ric8, while globally-diffusing Gβγ mediates their activation. We show that the predicted response at the level of Ras activation encodes sufficient ‘memory’ to eliminate the ‘back-of-the wave’ problem, and the effects of diffusion and cell shape on direction sensing are also investigated. In contrast with existing LEGI models of chemotaxis, the results do not require a disparity between the diffusion coefficients of the Ras activator GEF and the Ras inhibitor GAP. Since the signal pathways we study are highly conserved between Dicty and mammalian leukocytes, the model can serve as a generic one for direction sensing.

Significant Inter-Test Reliability across Approximate Number System Assessments.

The approximate number system (ANS) is the hypothesized cognitive mechanism that allows adults, infants, and animals to enumerate large sets of items approximately. Researchers usually assess the ANS by having subjects compare two sets and indicate which is larger. Accuracy or Weber fraction is taken as an index of the acuity of the system. However, as Clayton et al. (2015) have highlighted, the stimulus parameters used when assessing the ANS vary widely. In particular, the numerical ratio between the pairs, and the way in which non-numerical features are varied often differ radically between studies. Recently, Clayton et al. (2015) found that accuracy measures derived from two commonly used stimulus sets are not significantly correlated. They argue that a lack of inter-test reliability threatens the validity of the ANS construct. Here we apply a recently developed modeling technique to the same data set. The model, by explicitly accounting for the effect of numerical ratio and non-numerical features, produces dependent measures that are less perturbed by stimulus protocol. Contrary to their conclusion we find a significant correlation in Weber fraction across the two stimulus sets. Nevertheless, in agreement with Clayton et al. (2015) we find that different protocols do indeed induce differences in numerical acuity and the degree of influence of non-numerical stimulus features. These findings highlight the need for a systematic investigation of how protocol idiosyncrasies affect ANS assessments.

Maintaining ocular safety with light exposure, focusing on devices for optogenetic stimulation

Optogenetics methods are rapidly being developed as therapeutic tools for treating neurological diseases, in particular, retinal degenerative diseases. A critical component of the development is testing the safety of the light stimulation used to activate the optogenetic proteins. While the stimulation needs to be sufficient to produce neural responses in the targeted retinal cell class, it also needs to be below photochemical and photothermal limits known to cause ocular damage. The maximal permissible exposure is determined by a variety of factors, including wavelength, exposure duration, visual angle, pupil size, pulse width, pulse pattern, and repetition frequency. In this paper, we develop utilities to systematically and efficiently assess the contributions of these parameters in relation to the limits, following directly from the 2014 American National Standards Institute (ANSI). We also provide an array of stimulus protocols that fall within the bounds of both safety and effectiveness. Additional verification of safety is provided with a case study in rats using one of these protocols.

Space Takes Time: Concentration Dependent Output Codes from Primary Olfactory Networks Rapidly Provide Additional Information at Defined Discrimination Thresholds.

As odor concentration increases, primary olfactory network representations expand in spatial distribution, temporal complexity and duration. However, the direct relationship between concentration dependent odor representations and the psychophysical thresholds of detection and discrimination is poorly understood. This relationship is absolutely critical as thresholds signify transition points whereby representations become meaningful to the organism. Here, we matched stimulus protocols for psychophysical assays and intracellular recordings of antennal lobe (AL) projection neurons (PNs) in the moth Manduca sexta to directly compare psychophysical thresholds and the output representations they elicit. We first behaviorally identified odor detection and discrimination thresholds across an odor dilution series for a panel of structurally similar odors. We then characterized spatiotemporal spiking patterns across a population of individually filled and identified AL PNs in response to those odors at concentrations below, at, and above identified thresholds. Using spatial and spatiotemporal based analyses we observed that each stimulus produced unique representations, even at sub-threshold concentrations. Mean response latency did not decrease and the percent glomerular activation did not increase with concentration until undiluted odor. Furthermore, correlations between spatial patterns for odor decreased, but only significantly with undiluted odor. Using time-integrated Euclidean distance (ED) measures, we determined that added spatiotemporal information was present at the discrimination but not detection threshold. This added information was evidenced by an increase in integrated distance between the sub-detection and discrimination threshold concentrations (of the same odor) that was not present in comparison of the sub-detection and detection threshold. After consideration of delays for information to reach the AL we find that it takes ~120–140 ms for the AL to output identity information. Overall, these results demonstrate that as odor concentration increases, added information about odor identity is embedded in the spatiotemporal representation at the discrimination threshold.

Integration of electrophysiological recordings with single-cell RNA-seq data identifies neuronal subtypes.

Traditionally, neuroscientists have defined the identity of neurons by the cells' location, morphology, connectivity and excitability. However, the direct relationship between these parameters and the molecular phenotypes has remained largely unexplored. Here, we present a method for obtaining full transcriptome data from single neocortical pyramidal cells and interneurons after whole-cell patch-clamp recordings in mouse brain slices. In our approach, termed Patch-seq, a patch-clamp stimulus protocol is followed by the aspiration of the entire somatic compartment into the recording pipette, reverse transcription of RNA including addition of unique molecular identifiers, cDNA amplification, Illumina library preparation and sequencing. We show that Patch-seq reveals a close link between electrophysiological characteristics, responses to acute chemical challenges and RNA expression of neurotransmitter receptors and channels. Moreover, it distinguishes neuronal subpopulations that correspond to both well-established and, to our knowledge, hitherto undescribed neuronal subtypes. Our findings demonstrate the ability of Patch-seq to precisely map neuronal subtypes and predict their network contributions in the brain.

Blue Multifocal Pupillographic Objective Perimetry in Glaucoma.

This study investigated multifocal pupillographic objective perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. The diagnostic potential for glaucoma is compared between stimuli biased toward either cone input to these cells or their melanopsin response. Nineteen glaucoma patients and 24 normal subjects were tested using mfPOP stimulus protocols with either 33-ms yellow or 750-ms blue stimuli. Subjects' color discrimination was assessed using the Farnsworth 100-hue test. Pupillary responses were measured, and mixed-effects regression was used to quantify results. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. The mean reduction in moderate to severe glaucoma pupil responses using blue mfPOP stimuli was larger but more variable than that of the shorter yellow stimuli (blue: -1.32 dB [t(40) = -2.29; P = 0.027]; yellow: -0.93 dB [t(40) = -3.13; P = 0.003]). Color discrimination decreased significantly with age and glaucoma, with type III blue-yellow anomalies dominating. ROC analysis revealed similar diagnostic accuracies (AUC for eyes classified as moderate to severe; blue: 81.7%, yellow: 83.7). Slightly higher sensitivity and specificity were obtained using blue stimuli in mild disease (AUCs blue: 71.1, cf. yellow: 67.7), although this difference was not significant. In moderate to severe glaucoma, diagnostic accuracy of yellow and blue was similar, but blue stimuli showed limited ability to resolve scotomas. Blue mfPOP stimuli, however, may have advantages over yellow in detecting early glaucoma.

Effective Stimulus Parameters for Directed Locomotion in Madagascar Hissing Cockroach Biobot.

Swarms of insects instrumented with wireless electronic backpacks have previously been proposed for potential use in search and rescue operations. Before deploying such biobot swarms, an effective long-term neural-electric stimulus interface must be established, and the locomotion response to various stimuli quantified. To this end, we studied a variety of pulse types (mono- vs. bipolar; voltage- vs. current-controlled) and shapes (amplitude, frequency, duration) to parameters that are most effective for evoking locomotion along a desired path in the Madagascar hissing cockroach (G. portentosa) in response to antennal and cercal stimulation. We identified bipolar, 2 V, 50 Hz, 0.5 s voltage controlled pulses as being optimal for evoking forward motion and turns in the expected contraversive direction without habituation in ≈50% of test subjects, a substantial increase over ≈10% success rates previously reported. Larger amplitudes for voltage (1–4 V) and current (50–150 μA) pulses generally evoked larger forward walking (15.6–25.6 cm; 3.9–5.6 cm/s) but smaller concomitant turning responses (149 to 80.0 deg; 62.8 to 41.2 deg/s). Thus, the radius of curvature of the initial turn-then-run locomotor response (≈10–25 cm) could be controlled in a graded manner by varying the stimulus amplitude. These findings could be used to help optimize stimulus protocols for swarms of cockroach biobots navigating unknown terrain.

Real Time Monitoring of Electrostatic Potentials in the Vicinity of Electrodes Delivering Current Pulses Used in Neural Stimulation

Neural stimulation by metal electrodes such as Pt and its alloys and W has been used previously to evoke electrical activity in neurons1. This process involves passing short extracellular current pulses (ca. 100 µs) aimed at modifying the extracellular potential (Vext) and thereby altering the cell membrane potential. However, direct experimental measurements of Vext during such stimuli have been lacking. Theory suggests that Vext depends on both space and time. We have developed a method (ohmic microscopy) to measure Vext quantitatively with both spatial and temporal resolution, while passing current across noble metal electrodes during voltammetric scans.2-4 The present work extends application of this technique to current stimulus protocols commonly used in neural stimulation, including functional neural stimulation in clinical settings. EXPERIMENTAL Thin wall glass capillaries were pulled to a diameter of ca. 10 µm for each barrel, and filled with an aqueous 0.1 M H2SO4 solution. Microreference (μ-ref) Ag/AgCl electrodes were made by inserting Ag wires coated with a layer of AgCl (0.125 mm in diameter) formed by dipping the wire in a saturated KCl aqueous solution for at least 12 h. The μ-ref Ag/AgCl electrodes were mounted on individual holders connected in turn to individual micromanipulators. Pt disk (diameter 1.6mm) as working electrode, Pt wire as counter electrode, and Ag/AgCl(saturated) as reference electrode, 0.1M H2SO4 with their tips aligned along the normal to the center of the Pt disk (see Fig 1) at prescribed heights. A current pulse of a few mA was then applied to the Pt disk using a function generator (Agilent 33220A) coupled to a potentiostat (Autolab, PGSTAT302N, Nova 1.10, Metrohm). The time response of the potential difference between the two μ-ref electrodes, denoted as, Δφsol, amplified 10 times (Ina141, Texas instrument), was recorded on an oscilloscope (Agilent DSO-X 2014A). A schematic diagram of the instrument setup is shown is Fig. 1. RESULTS AND DISCUSSION For these experiments a current pulse of 5 mA, 100 μs in duration was applied across the Pt disk electrode (see red curve in Fig. 2), while recording the potential difference, Dϕ, across the two μ-ref Ag/AgCl electrodes placed at 1 mm, and 2mm normal to the disk along its center line (see blue curve, Fig. 2). As indicate therein, during the passage of current Dϕ was found to be ca. 62.5 mV. This value compares very well, i.e. slightly over 2%, with that predicted by Newman5, i.e. 61.2 mV. Excellent agreement was also found for other current values, duty cycles, and placement of the μ-ref Ag/AgCl electrodes. Efforts are underway to measure the response of dissociated neurons as a function of the placement of the electrodes and the stimulation parameters. ACKNOWLEDGEMENTS This work was supported by a Grant from NSF. REFERENCE D. R. Merrill, M. Bikson, J. G. R. Jefferys, J . Neurosci. Methods, 141 (2005), 171C. A. Cartier, D. Kumsa, Z. Feng, H. Zhu, D. A. Scherson, Anal. Chem. 84 (2012), 7080Y. Chen , A. Belianinov, D. A. Scherson, J. phy. Chem. C, 112 (2008), 8754M. Ignatowitz, E. Oesterschulze, App. Phy. Lett., 101 (2012), 251601J. Newman, J. Electrochem. Soc., 113 (1966), 501. Figure 1

Montreal SfNIRS conference shines light on the brain.

Montreal SfNIRS conference shines light on the brain.

Interactions Among Different Devices and Electrical Stimulus on the Electroejaculation of Captive Agoutis (Dasyprocta leporina).

The interactions among different electroejaculation devices associated with serial or continuous stimuli were investigated to improve the efficiency of the electroejaculation for semen collection in agoutis. Ten sexually matured male Dasyprocta leporina were restrained by the intramuscular administration of xylazine-ketamine association. Each individual was randomly subjected to four electroejaculation protocols, by combining two devices (one presenting longitudinal electrodes emitting square waves and other presenting ring electrodes emitting sine waves) and two electrical stimuli protocols (serial or continuous). A total of 40 attempts for electroejaculation were conducted in agoutis, being 10 per treatment. The most efficient treatment in providing ejaculates containing sperm (p<0.05) was that using and electroejaculator connected to a probe with ring electrodes and associated with serial stimuli (4/7; 57%). In spite of semen parameters obtained by sine waves were adequate for using the samples for assisted reproduction, higher values for sperm motility and functional membrane integrity were obtained in the use of the square wave, independently of the electric stimulation protocol used (p<0.05). In conclusion, we verified that the use of a device presenting a probe with ring electrodes and emitting sine waves, associated with a serial stimuli protocol, improves the efficiency for semen obtaining by electroejaculation in adults D.leporina.

Olfactory thresholds of the U.S. Population of home-dwelling older adults: development and validation of a short, reliable measure.

Current methods of olfactory sensitivity testing are logistically challenging and therefore infeasible for use in in-home surveys and other field settings. We developed a fast, easy and reliable method of assessing olfactory thresholds, and used it in the first study of olfactory sensitivity in a nationally representative sample of U.S. home-dwelling older adults. We validated our method via computer simulation together with a model estimated from 590 normosmics. Simulated subjects were assigned n-butanol thresholds drawn from the estimated normosmic distribution and based on these and the model, we simulated administration of both the staircase and constant stimuli methods. Our results replicate both the correlation between the two methods and their reliability as previously reported by studies using human subjects. Further simulations evaluated the reliability of different constant stimuli protocols, varying both the range of dilutions and number of stimuli (6–16). Six appropriately chosen dilutions were sufficient for good reliability (0.67) in normosmic subjects. Finally, we applied our method to design a 5-minute, in-home assessment of older adults (National Social Life, Health and Aging Project, or NSHAP), which had comparable reliability (0.56), despite many subjects having estimated thresholds above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli protocol is informative, and permits olfactory testing in previously inaccessible research settings.

Temporal Processing in Bistable Perception of the Necker Cube.

Perception of ambiguous figures is unstable and alternates repeatedly between possible interpretations. Some approaches to explaining this phenomenon have, so far, assumed low-level bottom-up mechanisms like adaptation and mutual inhibition of underlying neural assemblies. In contrast, less precise top-down approaches assume high-level attentional control mechanisms generalised across sensory modalities. In the current work we focused on specific aspects of the top-down approach. In a first study we used dwell times (periods of transiently stable percepts) and the parameters of dwell time distribution functions to compare the dynamics of perceptual alternations between visual (Necker cube) and auditory ambiguity (verbal transformation effect). In a second study we compared the endogenous alternation dynamics of the Necker cube with parameters from two attention tasks with different regimes of temporal dynamics. The first attention task (d2) is characterised by endogenous self-paced dynamics, similar to the dynamics underlying perceptual alternations of ambiguous figures, and we found clear correlations between dwell time parameters (Necker cube) and processing speed (d2 task). The temporal dynamics of the second (go/no-go) attention task, in contrast, are exogenously governed by the stimulus protocol, and we found no statistically significant correlation with the Necker cube data. Our results indicate that both perceptual instability and higher-level attentional tasks are linked to endogenous brain dynamics on a global coordinating level beyond sensory modalities.

Dopamine D1 and D5 receptors modulate spike timing-dependent plasticity at medial perforant path to dentate granule cell synapses.

Although evidence suggests that DA modulates hippocampal function, the mechanisms underlying that dopaminergic modulation are largely unknown. Using perforated-patch electrophysiological techniques to maintain the intracellular milieu, we investigated how the activation of D1-type DA receptors regulates spike timing-dependent plasticity (STDP) of the medial perforant path (mPP) synapse onto dentate granule cells. When D1-type receptors were inhibited, a relatively mild STDP protocol induced LTP only within a very narrow timing window between presynaptic stimulation and postsynaptic response. The stimulus protocol produced timing-dependent LTP (tLTP) only when the presynaptic stimulation was followed 30 ms later by depolarization-induced postsynaptic action potentials. That is, the time between presynaptic stimulation and postsynaptic response was 30 ms (Δt = +30 ms). When D1-type receptors were activated, however, the same mild STDP protocol induced tLTP over a much broader timing window: tLTP was induced when -30 ms ≤ Δt ≤ +30 ms. The result indicated that D1-type receptor activation enabled synaptic potentiation even when postsynaptic activity preceded presynaptic stimulation within this Δt range. Results with null mice lacking the Kv4.2 potassium channel and with the potassium channel inhibitor, 4-aminopyridine, suggested that D1-type receptors enhanced tLTP induction by suppressing the transient IA-type K(+) current. Results obtained with antagonists and DA receptor knock-out mice indicated that endogenous activity of both D1 and D5 receptors modulated plasticity in the mPP. The DA D5 receptors appeared particularly important in regulating plasticity of the mPP onto the dentate granule cells.

Alouatta trichromatic color vision: cone spectra and physiological responses studied with microspectrophotometry and single unit retinal electrophysiology.

The howler monkeys (Alouatta sp.) are the only New World primates to exhibit routine trichromacy. Both males and females have three cone photopigments. However, in contrast to Old World monkeys, Alouatta has a locus control region upstream of each opsin gene on the X-chromosome and this might influence the retinal organization underlying its color vision. Post-mortem microspectrophotometry (MSP) was performed on the retinae of two male Alouatta to obtain rod and cone spectral sensitivities. The MSP data were consistent with only a single opsin being expressed in each cone and electrophysiological data were consistent with this primate expressing full trichromacy. To study the physiological organization of the retina underlying Alouatta trichromacy, we recorded from retinal ganglion cells of the same animals used for MSP measurements with a variety of achromatic and chromatic stimulus protocols. We found MC cells and PC cells in the Alouatta retina with similar properties to those previously found in the retina of other trichromatic primates. MC cells showed strong phasic responses to luminance changes and little response to chromatic pulses. PC cells showed strong tonic response to chromatic changes and small tonic response to luminance changes. Responses to other stimulus protocols (flicker photometry; changing the relative phase of red and green modulated lights; temporal modulation transfer functions) were also similar to those recorded in other trichromatic primates. MC cells also showed a pronounced frequency double response to chromatic modulation, and with luminance modulation response saturation accompanied by a phase advance between 10–20 Hz, characteristic of a contrast gain mechanism. This indicates a very similar retinal organization to Old-World monkeys. Cone-specific opsin expression in the presence of a locus control region for each opsin may call into question the hypothesis that this region exclusively controls opsin expression.

Neuroimaging paradigms for tonotopic mapping (I): The influence of sound stimulus type

Although a consensus is emerging in the literature regarding the tonotopic organisation of auditory cortex in humans, previous studies employed a vast array of different neuroimaging protocols. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between stimulus protocols involving jittered tone sequences with either a narrowband, broadband, or sweep character in order to evaluate their suitability for the purpose of tonotopic mapping. Data-driven analysis techniques were used to identify cortical maps related to sound-evoked activation and tonotopic frequency tuning. Principal component analysis (PCA) was used to extract the dominant response patterns in each of the three protocols separately, and generalised canonical correlation analysis (CCA) to assess the commonalities between protocols. Generally speaking, all three types of stimuli evoked similarly distributed response patterns and resulted in qualitatively similar tonotopic maps. However, quantitatively, we found that broadband stimuli are most efficient at evoking responses in auditory cortex, whereas narrowband and sweep stimuli offer the best sensitivity to differences in frequency tuning. Based on these results, we make several recommendations regarding optimal stimulus protocols, and conclude that an experimental design based on narrowband stimuli provides the best sensitivity to frequency-dependent responses to determine tonotopic maps. We forward that the resulting protocol is suitable to act as a localiser of tonotopic cortical fields in individuals, or to make quantitative comparisons between maps in dedicated tonotopic mapping studies.

Violence-related PTSD and neural activation when seeing emotionally charged male-female interactions.

Post-traumatic stress disorder (PTSD) is a disorder that involves impaired regulation of the fear response to traumatic reminders. This study tested how women with male-perpetrated interpersonal violence-related PTSD (IPV-PTSD) differed in their brain activation from healthy controls (HC) when exposed to scenes of male-female interaction of differing emotional content. Sixteen women with symptoms of IPV-PTSD and 19 HC participated in this study. During magnetic resonance imaging, participants watched a stimulus protocol of 23 different 20 s silent epochs of male-female interactions taken from feature films, which were neutral, menacing or prosocial. IPV-PTSD participants compared with HC showed (i) greater dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) activation in response to menacing vs prosocial scenes and (ii) greater anterior cingulate cortex (ACC), right hippocampus activation and lower ventromedial prefrontal cortex (vmPFC) activty in response to emotional vs neutral scenes. The fact that IPV-PTSD participants compared with HC showed lower activity of the ventral ACC during emotionally charged scenes regardless of the valence of the scenes suggests that impaired social perception among IPV-PTSD patients transcends menacing contexts and generalizes to a wider variety of emotionally charged male-female interactions.

A novel Dual Probe Complex Trial Protocol for detection of concealed information.

In simply guilty (SG), countermeasure-using guilty (CM), and innocent (IN) subjects, a new concealed information test, the P300-based Dual Probe Complex Trial Protocol was tested in a mock crime scenario. It combines an oddball protocol with two stimuli (probe, irrelevant) and another with three stimuli (probe, irrelevant, target) into one trial, doubling detected mock crime information per unit time, compared to previous protocols. Probe-irrelevant amplitude differences were significant in SG and CM, but not IN subjects. On a measure from both two and three stimulus protocol parts of the Dual Probe Complex Trial Protocol trial, accuracy was 94.7% (based on a .9 bootstrap criterion). The criterion-independent area (AUC) under the receiver operating characteristic (from signal detection theory) measuring SG and CM versus IN discriminability averaged .92 (in a range of 0.5-1.0). Countermeasures enhanced irrelevant (not probe) P300s in CM groups.

The actual intrinsic excitability of granular cells determines the ruling neurovascular coupling mechanism in the rat dentate gyrus.

Paired-pulse stimulation of the perforant pathway was used to study the relation between granular cell activity and the resultant fMRI response in the rat dentate gyrus. By varying the interpulse interval (IPI), paired-pulse stimulations caused: a depression (20 ms IPI), a facilitation (100 ms IPI), a mixture of depression and facilitation (30 ms IPI), or no change (500 ms IPS) in the second response. Eight identical paired pulses were applied during one stimulation train and the evoked field potentials and generated fMRI responses were measured simultaneously. Application of consecutive stimulation trains caused time-dependent variations in electrophysiological and fMRI responses, which were characteristic for each stimulus protocol. Depending on the IPI, the magnitude of the fMRI response either correlated strongly with or was apparently unrelated to the spiking or postsynaptic activity of the granular cells. A strong relation between spiking activity and resultant fMRI response was only found when the stimulation protocol caused an increase in the recorded population spike latency. If the latency was decreased, the fMRI response was more closely related to the applied input activity. Perforant pathway fibers monosynaptically activate granular cells, so variations in population spike latencies reflect changes in their intrinsic excitability. Therefore, during increased intrinsic excitability, signaling cascades upstream of the granular cells determine the fMRI response, whereas granular cell activity-related mechanisms control the fMRI response during decreased intrinsic excitability.