Full Stimulus Research Articles

An adaptive Bayesian algorithm for efficient auditory brainstem response threshold estimation: Numerical validation

The auditory brainstem response (ABR) can be used to estimate the hearing threshold of animals or human subjects who are unable to respond to behavioral measures. However, ABR can be time-intensive and is vulnerable to human subjectivity while interpreting the waveforms. An adaptive procedure has been developed to efficiently and objectively estimate ABR threshold. The procedure iteratively fits a Gaussian process (GP) model to the ABR waveforms collected so far and optimizes the subsequent stimulus. The algorithm was validated through numerical simulation using pre-collectedhuman ABR at 0.5, 1.0, 2.0, and 4.0 kHz with levels from below threshold to 90 dB in 5 dB increments from a cohort of normal-hearing listeners. This led to a full stimulus space of approximately 55 stimuli per test ear. For each test ear, the ABR threshold was estimated by human raters based on the entire stimulus space. The ABR threshold was also estimated using the adaptive procedure, which iteratively sampled a subset (∼35%) of the stimulus space. At the end of the adaptive procedure, the fitted GP model was able to capture the individual differences in waveform morphology between listeners. Furthermore, the threshold estimates from repeated runs of the adaptive procedure demonstrated adequate test-retest reliability.

The Mechanical Properties of in Situ Canine Skeletal Muscle.

This study was undertaken to determine if fiber arrangement was responsible for differences in the whole muscle mechanical properties. Experiments were carried out in situ in blood perfused dog skeletal muscles at approximately normal body temperature between 36° and 38°C. The following mechanical relationships were studied using a pneumatic muscle lever to measure Tension (P), length (L) and dP/dt: and dL/dt with a high frequency oscillograph (500–1000 Hz): 1.) Length:Tension; 2.) Force:Velocity; and 3.) Stress:Strain of Series Elastic. Electron microscopy and fiber typing were done as adjunctive studies. Muscles were stimulated by direct nerve stimulation with 0.1msec stimuli at a rate of 1 impulse per second for twitch contractions, or in 200 msec bursts of 100 Hz 0.1 msec stimuli for brief tetanic contractions. The pennate short fibered gastrocnemius plantaris developed 1.0 kg/g of tension during brief tetanic stimulation, at optimal length (Lo) with full stimulus voltage, while the parallel long fibered semitendinosus developed 0.5 kg/g under the same conditions. The Length:Tension relationship for these two muscles was qualitatively similar but quantitatively different. The Force:Velocity relationship (ΔL/L0 vs. P/P0) for both muscles were also qualitatively similar and could be described by the previously proposed rectangular hyperbola but a better predicted fit to the observed data could be produced by adding a descending exponential function to the rectangular hyperbola. Unlike previous studies, the Stress:Strain properties of the series elastic component measured by quick release (ΔL/Li vs. ΔP/Po) were linear and gastrocnemius was 25 per cent higher than the semitendinosus. Overall, both muscles were found to have mechanical properties that differed little from the previously reported literature for amphibian, cardiac and small mammalian muscles studied by others in vitro. The major differences that we found were in the shapes of the force:velocity curve of the contractile component, and the Stress:Strain curve of series elastic component. Equations and explanations for these differences are devised and presented.

TEACHING SYMBOLIC RELATIONS IN DOWN SYNDROME THROUGH EQUIVALENCE-BASED INSTRUCTION: A CASE STUDY

A procedure for establishing equivalence classes in a participant with Down syndrome was implemented. The classes were composed of written words (A), pictorial representations (B), digit numbers (C), and auditory words (D) representing metro stations. In the training phase, we implemented a successful procedure for enhancing perceptual discrimination of written words when presented as sample stimuli (A), and we established a reduced number of stimulus relations: AB, BC, DA, from which the participant was able to derive full stimulus classes that included derived relations between stimuli that had not been trained before: BA, CB, AC, CA, DB, and DC. The study encompassed a total of 7 sessions, and by the end these, the participant showed correct mappings between written words, pictures, auditory words, and digits. We detail adaptations to traditional training procedures that facilitated learning in the participant with Down syndrome. We argue that procedures based on equivalence instruction are beneficial for the establishment of symbolic and communicative repertoires in individuals with developmental disabilities.

Characterization of 3,4-methylenedioxypyrovalerone discrimination in female Sprague-Dawley rats.

3,4-Methylenedioxypyrovalerone (MDPV), one of several synthetic cathinones, is a popular constituent of illicit 'bath salts'. In preclinical studies utilizing drug discrimination methods with male rodents, MDPV has been characterized as similar to both cocaine and 3,4-methylenedioxymethamphetamine-hydrochloride (MDMA). Whereas few drug discrimination studies have utilized female rats, the current study evaluated the discriminative stimulus effects of MDPV in 12 adult female Sprague-Dawley rats trained to discriminate 0.5 mg/kg MDPV from saline under a fixed ratio 20 schedule of food reinforcement. Stimulus substitution was assessed with MDPV and its enantiomers, other synthetic cathinones [alpha pyrrolidinopentiophenone-hydrochloride(α-PVP), 4-methylmethcathinone (4-MMC)], other dopamine agonists (cocaine, [+)-methamphetamine] and serotonin agonists [MDMA, lysergic acid diethylamide (LSD)] Stimulus antagonism was assessed with the dopamine D1 receptor antagonist, Sch 23390 and the D2 receptor antagonist, haloperidol. Cocaine and (+)-methamphetamine engendered full stimulus generalization to MDPV with minimal effects on response rate. LSD produced partial substitution, whereas MDMA and 4-MMC produced complete substitution, and all these serotonergic compounds produced dose-dependent response suppression. (S)-MDPV and α-PVP engendered full substitution with similar potency to the racemate, while (R)-MDPV failed to substitute up to 5 mg/kg. Both Sch 23390 and haloperidol attenuated the discrimination of low MDPV doses and essentially shifted the dose-response curve to the right but failed to block discrimination of the training dose. These findings are generally consistent with previous reports based exclusively on male rodents. Moreover, they confirm the contribution of dopaminergic mechanisms but do not rule out the possible contribution of other neurotransmitter actions to the interoceptive stimulus effects of MDPV.

A comparative study of facial emotion recognition pattern and its determinants in patients of alcohol dependence syndrome versus matching controls

Background: Facial emotional recognition plays a pivotal role in human interactions and behavior. Long-term alcohol use leads to brain dysfunction that causes impairment in social cognitive abilities including facial emotional recognition. Objectives: Our study was aimed to assess the facial emotional recognition pattern in patients with alcohol dependence syndrome (ADS) and compared with that of matching controls and to study the sociodemographic and clinical correlates of facial emotional recognition in ADS. Setting and Design: This cross-sectional study was conducted at a tertiary care teaching hospital for a period of 1½ years. Fifty participants having ADS and fifty controls were included in the study. Materials and Methods: Fifty participants having ADS and fifty controls were included in the study. In the group with ADS, a semi-structured pro forma was used to collect the sociodemographic and clinical profile. Rating scales such as Severity of Alcohol Dependence Questionnaire, the Clinical Institute Withdrawal Assessment for Alcohol scale-revised, and facial emotion recognition test (FERT) were administered. For the control group, FERT was administered after collecting the data regarding sociodemographic profile and clinical variables. Results: It was observed a significant impairment in FERT scores in individuals having ADS (mean score = 19.93 ± 7.67) when compared to the control population (mean score = 32.73 ± 4.96T-test = −10.86; P < 0.001). Lower scores on FERT were observed in persons with severe alcohol dependence (one-way ANOVA = 41.79, P < 0.001). Post hoc Tukey testing showed the difference between groups having moderate-to-severe dependence (P < 0.001) and mild-to-severe dependence (P < 0.001). Conclusions: Significant impairment in facial emotional recognition skills were observed in patients having ADS. The subjects in ADS group were able to identify happy and angry emotions better while facing difficulties in identifying sad and fear full stimulus.

Predictive Validity of Thin Slices of Verbal and Nonverbal Behaviors: Comparison of Slice Lengths and Rating Methodologies

Thin slices, or excerpts of behavior, are commonly used by researchers to represent behaviors in their full stimulus. The present study asked how slices of different lengths and locations, as well as different measurement methodologies, influence correlations between the measured behavior and different variables (predictive validity). We collected self-rated, perceiver-rated, and objectively measured data on 60 participants who participated in a 5-min interaction with a confederate on video. These videos were split into five 1-min slices and rated for verbal and nonverbal behaviors via global impressions, using the same rater for all five slices and also using a different rater for each slice. For single slices, results indicated no clear pattern for optimal slice locations. In general, single slices had weaker predictive validity than the total. Slices of 2 or 3 min were, in general, equal to 5-min total in predictive validity. The magnitude of correlations was similar when same versus different coders were used, and the predictive validity correlations of the two methods covaried strongly across behavior-outcome variable combinations.

A real-time marker of object-based attention in the human brain. A possible component of a “gate-keeping mechanism” performing late attentional selection in the Ventro-Lateral Prefrontal Cortex

The decision to process an incoming stimulus attentively - and to trigger a follow-up cascade of high-level processes - is strategic for the human brain as it becomes transiently unavailable to subsequent stimulus processing. In this study, we set to identify brain networks that carry out such evaluations. We therefore assessed the time-course of neural responses with intracerebral EEG in human patients during an attentional reading task, contrasting to-be-attended vs. to-be-ignored items. We measured High-Frequency Activity [50–150 ​Hz] as a proxy of population-level spiking activity and we identified a crucial component of a Gate-Keeping Mechanism bilateral in the mid-Ventro-Lateral Prefrontal Cortex (VLPFC), at the interplay of the Ventral and Dorsal Attention Networks, that selectively reacts before domain specialized cortical regions that engage in full stimulus analysis according to task demands.

The Virtual-Environment-Foraging Task enables rapid training and single-trial metrics of rule acquisition and reversal in head-fixed mice

Behavioural flexibility is an essential survival skill, yet our understanding of its neuronal substrates is still limited. While mouse research offers unique tools to dissect the neuronal circuits involved, the measurement of flexible behaviour in mice often suffers from long training times, poor experimental control, and temporally imprecise binary (hit/miss) performance readouts. Here we present a virtual-environment task for mice that tackles these limitations. It offers fast training of vision-based rule reversals (~100 trials per reversal) with full stimulus control and continuous behavioural readouts. By generating multiple non-binary performance metrics per trial, it provides single-trial estimates not only of response accuracy and speed, but also of underlying processes like choice certainty and alertness (discussed in detail in a companion paper). Based on these metrics, we show that mice can predict new task rules long before they are able to execute them, and that this delay varies across animals. We also provide and validate single-trial estimates of whether an error was committed with or without awareness of the task rule. By tracking in unprecedented detail the cognitive dynamics underlying flexible behaviour, this task enables new investigations into the neuronal interactions that shape behavioural flexibility moment by moment.

Was That Painful or Nonpainful? The Sensation and Pain Rating Scale Performs Well in the Experimental Context

In experiments on pain, participants are frequently exposed to nonpainful and painful stimuli; however, the conventional pain-rating scales lack a nonpainful range and a clear point of transition from nonpainful to painful events. The Sensation and Pain Rating Scale (SPARS) assesses the full stimulus intensity range, extending from no sensation (rating: –50) to worst pain imaginable (rating: +50), and it explicitly identifies pain threshold (rating: 0). Here, we tested the SPARS in 2 experiments by using laser heat stimuli to establish its stimulus–response characteristics (Experiment 1, N = 19, 13 stimulus intensities applied 26 times each across a 1–4 J range), and compared it to 0 to 100 scales that assess nonpainful (0: no sensation, 100: pain) and painful (0: no pain, 100: worst pain imaginable) events (Experiment 2, N = 7, 9 stimulus intensities applied 36 times each across a 1.5–4.5 J range). Despite high inter- and intraindividual variations, we found a reasonably consistent curvilinear stimulus–response relationship (the curve flattens around pain threshold), with stable response characteristics across the range of the scale. The SPARS ratings transformed to a 0 to 100 range tended to be lower than the 0 to 100 pain rating scale in the noxious stimulus intensity range and greater than the 0 to 100 nonpainful sensation scale in the non-noxious stimulus range, likely reflecting differences in scale dimensionality. The SPARS overcomes limitations in scale range inherent to conventional pain rating scales. As such, it is well suited to experimental studies that must quantify a wider range of perceptual intensity or distinguish between painful and nonpainful events. PerspectiveThis article presents the stimulus–response characteristics of a new scale designed to allow participants to rate a range of nonpainful and painful stimuli. The scale could be useful for research that involves exposing participants to a range of stimulation intensities or requires a clear distinction between nonpainful and painful events.

The epigenetic modification during the induction of Foxp3 with sodium butyrate

Context: CD4 + CD25+ regulatory T (Treg) lymphocytes are critical for immune homeostasis. Foxp3 (Forkhead Box protein P3) is always considered as a marker of function and identities determination of Treg cells because of special occurring in Treg cell. People who lack Treg cells or have a low expression of Foxp3 gene will suffer fatal autoimmunity. Scientists are trying to use Treg cells as a treatment for autoimmune disease, such as systemic lupus erythematosus.Objective: Our objective was to induce Foxp3 + CD4+ T cells from naïve CD4 + T cells isolated from C57 mice spleen in vitro using stimuli that include the short chain fatty acid sodium butyrate. Furthermore, to explore the relationship between Foxp3+ T cells induction and epigenetic modification, by observing the changes of Foxp3, Ezh2 (Enhancer of Zeste Homolog 2) and phosphorylated Ezh2 in the induced Treg cells.Materials and methods: The naïve CD4+ T cells were separated from C57 mice spleen by immunomagnetic separation. Anti-CD28, anti-CD3, IL-2, TGF-β1, and sodium butyrate were added with proper concentration to induce Foxp3 expression during 72 hours. Then, we observed the effect of GSK126 (Ezh2 inhibitor) on the induction within the same over 72 hours duration. Then, western blot and Q-PCR were used to see the changes in gene/protein expression of Foxp3, Ezh2, and phosphorylated Ezh2.Results: According to our results, group 3 that received full stimulus had a significant higher level of Foxp3 and Ezh2 expression (p < .05, comparing with group 1,2) and adding 5 mM sodium butyrate to the full stimulus (group 5) increased significantly the induction of Foxp3 and Ezh2 than control group and higher concentration group (p < .05, comparing with group 3,4, 6). The gene and protein expression of Foxp3 and Ezh2 both were enhanced in group 5 (p < .05 comparing with group 3). However, phosphorylated Ezh2 decreased in group 5 (p < .05 comparing with group3). Sodium butyrate removed part inhibition of GSK126, result in Foxp3 and Ezh2 expression (p < .05, p < .01, comparing with group7).Conclusion: In this study, we were able to transform CD4 + T cells into CD4 + Foxp3 + T cell by using stimulus like antibodies (anti-CD28, anti-CD3) and cytokines (IL-2, TGF-β1). Sodium butyrate contributes to CD4 + Foxp3 + T cell induction in vitro and at an optimum concentration of 5 mM. Sodium butyrate promotes expression of Ezh2 and Fxop3 of T cells in vitro; in addition, to lowering relative expression of phosphorylated Ezh2 probably be influencing some pathways like PI3K-Akt. Epigenetic modification is also thought to take essential part into the upregulation of Foxp3 from naïve CD4 + Tcells.

Sequential dependencies in pitch judgments.

Studies that measure pitch discrimination relate a subject's response on each trial to the stimuli presented on that trial, but there is evidence that behavior depends also on earlier stimulation. Here, listeners heard a sequence of tones and reported after each tone whether it was higher or lower in pitch than the previous tone. Frequencies were determined by an adaptive staircase targeting 75% correct, with interleaved tracks to ensure independence between consecutive frequency changes. Responses for this specific task were predicted by a model that took into account the frequency interval on the current trial, as well as the interval and response on the previous trial. This model was superior to simpler models. The dependence on the previous interval was positive (assimilative) for all subjects, consistent with persistence of the sensory trace. The dependence on the previous response was either positive or negative, depending on the subject, consistent with a subject-specific suboptimal response strategy. It is argued that a full stimulus + response model is necessary to account for effects of stimulus history and obtain an accurate estimate of sensory noise.

Neurophysiological evidence (ERPs) for hemispheric processing of facial expressions of emotions: Evidence from whole face and chimeric face stimuli

ABSTRACTThis study was designed to investigate the patterns of electrophysiological responses of early emotional processing at frontocentral sites in adults and to explore whether adults’ activation patterns show hemispheric lateralization for facial emotion processing. Thirty-five adults viewed full face and chimeric face stimuli. After viewing two faces, sequentially, participants were asked to decide which of the two faces was more emotive. The findings from the standard faces and the chimeric faces suggest that emotion processing is present during the early phases of face processing in the frontocentral sites. In particular, sad emotional faces are processed differently than neutral and happy (including happy chimeras) faces in these early phases of processing. Further, there were differences in the electrode amplitudes over the left and right hemisphere, particularly in the early temporal window. This research provides supporting evidence that the chimeric face test is a test of emotion processing that elicits right hemispheric processing.

Time-compressed preplay of anticipated events in human primary visual cortex

Perception is guided by the anticipation of future events. It has been hypothesized that this process may be implemented by pattern completion in early visual cortex, in which a stimulus sequence is recreated after only a subset of the visual input is provided. Here we test this hypothesis using ultra-fast functional magnetic resonance imaging to measure BOLD activity at precisely defined receptive field locations in visual cortex (V1) of human volunteers. We find that after familiarizing subjects with a spatial sequence, flashing only the starting point of the sequence triggers an activity wave in V1 that resembles the full stimulus sequence. This preplay activity is temporally compressed compared to the actual stimulus sequence and remains present even when attention is diverted from the stimulus sequence. Preplay might therefore constitute an automatic prediction mechanism for temporal sequences in V1.

Diagnostic Ability of Automated Pupillography in Glaucoma

ABSTRACTPurpose: To evaluate the diagnostic ability of automated pupillography measurements in glaucoma and study the effect of inter-eye asymmetry in glaucomatous damage on the diagnostic ability.Methods: In an observational, cross-sectional study, 47 glaucoma patients and 42 control subjects underwent automated pupillography using a commercially available device. Diagnostic abilities of the pupillary response measurements were evaluated using area under receiver operating characteristic (ROC) curves (AUC) and sensitivities at fixed specificities. Influence of inter-eye asymmetry in glaucoma [inter-eye mean deviation (MD) difference on visual fields (VF)] on the diagnostic ability of pupillography parameters was evaluated by ROC regression approach.Results: The AUCs of automated pupillography parameters ranged from 0.60 (amplitude score with peripheral blue stimulus) to 0.82 (amplitude score with full field white stimulus, Amp-FF-W). Sensitivity at 95% specificity ranged between 5% (amplitude score with full field blue stimulus) and 45% (amplitude score with full field green stimulus). Inter-eye MD difference significantly affected the diagnostic performance of automated pupillography parameters (p < 0.05). AUCs of Amp-FF-W at inter-eye MD difference of 0 dB, 5 dB, 10 dB and 15 dB were 0.71, 0.80, 0.87 and 0.93, respectively, according to the regression model. The corresponding sensitivities at 95% specificity were 20%, 34%, 50% and 66%, respectively.Conclusions: The diagnostic abilities of even the best automated pupillography parameters were only moderate in glaucoma. The performance of these pupillography measurements in detecting glaucoma significantly increased with greater inter-eye asymmetry in the glaucomatous damage.

Alpha suppression and connectivity modulations in left temporal and parietal cortices index partial awareness of words

The partial awareness hypothesis is a theoretical proposal that recently provided a reconciling solution to graded and dichotomous accounts of consciousness. It suggests that we can become conscious of distinct properties of an object independently, ranging from low-level features to complex forms of representation. We investigated this hypothesis using classic visual word masking adapted to a near-threshold paradigm. The masking intensity was adjusted to the individual perception threshold, at which individual alphabetical letters, but not words, could be perceived in approximately half of the trials. We confined perception to a pre-lexical stage of word processing that corresponded to a clear condition of partial awareness. At this level of representation, the stimulus properties began to emerge within consciousness, yet they did not escalate to full stimulus awareness. In other words, participants were able to perceive individual letters, while remaining unaware of the whole letter strings presented. Cortical activity measured with MEG was compared between physically identical trials that differed in perception (perceived, not perceived). We found that compared to no awareness, partial awareness of words was characterized by suppression of oscillatory alpha power in left temporal and parietal cortices. The analysis of functional connectivity with seeds based on the power effect in these two regions revealed sparse connections for the parietal seed, and strong connections between the temporal seed and other regions of the language network. We suggest that the engagement of language regions indexed by alpha power suppression is responsible for establishing and maintaining conscious representations of individual pre-lexical units.

The Discriminative Stimulus Effects of the Neurotensin NTS1 Receptor Agonist PD149163 in Rats: Stimulus Generalization Testing with Dopamine D1 and D2 Receptor Ligands

Brain-penetrant neurotensin NTS1 receptor agonists produce antipsychotic drug-like effects in animal models, including inhibition of conditioned avoidance responding and reversal of psychostimulant-induced hyperactivity and stereotypy. Allosteric interactions between NTS1 receptors and dopamine D2 receptors may account for some of these antipsychotic effects. In order to determine the role that dopamine receptors may play in the behavioral effects produced by activation of NTS1 receptors, a drug discrimination approach was used in rats to evaluate the potential mediation of NTS1 receptor agonist stimulus effects by dopamine D1 and D2 receptors. Rats were trained to discriminate either the NTS1 receptor agonist PD149163, the D1 receptor agonist SKF81297, or the D2 receptor agonist quinpirole from vehicle in a two choice drug discrimination task. Full stimulus generalization occurred from PD149163 to the typical antipsychotic drug and D2 receptor-preferring antagonist haloperidol. However, stimulus generalization did not occur from SKF81297 or quinpirole to PD149163. The discriminative cue for SKF91297 and quinpirole was fully blocked the D1 receptor antagonist SCH23390 and the D2/3 receptor antagonist raclopride, respectively. Cross generalization did not occur between SKF91297 and quinpirole. Based on these findings, the stimulus effects of PD149163 may be mediated, in part, through D2 receptor antagonism, but this may only be evident when PD149163 is used as the training drug.

Vowel identification by cochlear implant users: Contributions of static and dynamic spectral cues

Previous research has shown that normal hearing listeners can identify vowels in syllables on the basis of either quasi-static or dynamic spectral cues; however, it is not known how well cochlear implant (CI) users with current-generation devices can make use of these cues. The present study assessed vowel identification in adult CI users and a comparison group of young normal hearing (YNH) listeners. Stimuli were naturally spoken /dVd/ syllables and modified syllables that retained only quasi-static spectral cues from an 80-ms segment of the vowel center ("C80" stimuli) or dynamic spectral cues from two 20-ms segments of the vowel edges ("E20" stimuli). YNH listeners exhibited near-perfect performance for the unmodified (99.8%) and C80 (92.9%) stimuli and maintained good performance for the E20 stimuli (70.2%). CI users exhibited poorer average performance than YNH listeners for the Full stimuli (72.3%) and proportionally larger reductions in performance for the C80 stimuli (41.8%) and E20 stimuli (29.0%). Findings suggest that CI users have difficulty identifying vowels on the basis of spectral cues in the absence of duration cues, and have limited access to brief dynamic spectral cues. Error analyses suggest that CI users may rely strongly on vowel duration cues when those cues are available.

A set of 265 pictures standardized for studies of the cognitive processing of temporal and causal order information

Planning, predicting, reasoning, and acting often depend crucially on the correct encoding and application of knowledge concerning the temporal and causal ordering of events. Yet no pictorial stimulus set is optimized for investigating the processing of temporal and causal order information. We introduce a novel stimulus set of 265 black-and-white line drawings depicting a diverse array of recognizable events. Most of the images in the stimulus set (N = 222) share a thematic or conceptual association with one other image in the set, and the stimuli were created and extensively normed such that the image pairs vary in the degrees to which they share a causal, ordered relation with one another. The stimuli were standardized in a series of normative tasks, including concept/noun/verb agreement, perceived frequency, visual similarity, and indexes of three features of causal associations between events (i.e., temporal proximity, exclusivity, and priority). Both younger adults (ages 18-30 years) and older adults (ages 60-80 years) contributed normative data, allowing for broad applications of the stimuli to the study of normal and age-related changes in the encoding, retention, and retrieval of information regarding temporal and causal order. Complete normative data sets are available in the online supplemental materials, and the full stimulus set is available by contacting the first author.

Reduction of the perceptual field for inverted faces:evidence from gaze contingency with full view stimuli

Reduction of the perceptual field for inverted faces:evidence from gaze contingency with full view stimuli

Context Matters: The Illusive Simplicity of Macaque V1 Receptive Fields

Even in V1, where neurons have well characterized classical receptive fields (CRFs), it has been difficult to deduce which features of natural scenes stimuli they actually respond to. Forward models based upon CRF stimuli have had limited success in predicting the response of V1 neurons to natural scenes. As natural scenes exhibit complex spatial and temporal correlations, this could be due to surround effects that modulate the sensitivity of the CRF. Here, instead of attempting a forward model, we quantify the importance of the natural scenes surround for awake macaque monkeys by modeling it non-parametrically. We also quantify the influence of two forms of trial to trial variability. The first is related to the neuron’s own spike history. The second is related to ongoing mean field population activity reflected by the local field potential (LFP). We find that the surround produces strong temporal modulations in the firing rate that can be both suppressive and facilitative. Further, the LFP is found to induce a precise timing in spikes, which tend to be temporally localized on sharp LFP transients in the gamma frequency range. Using the pseudo R2 as a measure of model fit, we find that during natural scene viewing the CRF dominates, accounting for 60% of the fit, but that taken collectively the surround, spike history and LFP are almost as important, accounting for 40%. However, overall only a small proportion of V1 spiking statistics could be explained (R2∼5%), even when the full stimulus, spike history and LFP were taken into account. This suggests that under natural scene conditions, the dominant influence on V1 neurons is not the stimulus, nor the mean field dynamics of the LFP, but the complex, incoherent dynamics of the network in which neurons are embedded.