Evidence for dissociation between the perceptual and visuomotor systems in humans

When a visual stimulus is continuously moved behind a small stationary window, the window appears displaced in the direction of motion of the stimulus. In this study we showed that the magnitude of this illusion is dependent on (i) whether a perceptual or visuomotor task is used for judging the location of the window, (ii) the directional signature of the stimulus, and (iii) whether or not there is a significant delay between the end of the visual presentation and the initiation of the localization measure. Our stimulus was a drifting sinusoidal grating windowed in space by a stationary, two-dimensional, Gaussian envelope (σ=1 cycle of sinusoid). Localization measures were made following either a short (200 ms) or long (4.2 s) post-stimulus delay. The visuomotor localization error was up to three times greater than the perceptual error for a short delay. However, the visuomotor and perceptual localization measures were similar for a long delay. Our results provide evidence in support of the hypothesis that separate cortical pathways exist for visual perception and visually guided action and that delayed actions rely on stored perceptual information.

Humans assume a mixture of diffuse and point-source lighting when viewing sinusoidal shading patterns

Observers perceive sinusoidal shading patterns as being due to sinusoidally corrugated surfaces, and perceive surface peaks to be offset from luminance maxima by between zero and 1/4 wavelength. This offset varies with grating orientation. Physically, the shading profile of a sinusoidal surface will be approximately sinusoidal, with the same spatial frequency as the surface, only when: (A) it is lit suitably obliquely by a point source, or (B) the light source is diffuse and hemispherical--the 'dark is deep' rule applies. For A, surface peaks will be offset by 1/4 wavelength from the luminance maxima; for B, this offset will be zero. As the sum of two same-frequency sinusoids with different phases is a sinusoid of intermediate phase, our results suggest that observers assume a mixture of two light sources whose relative strength varies with grating orientation. The perceived surface offsets imply that gratings close to horizontal are taken to be lit by a point source; those close to vertical by a diffuse source. [Supported by EPSRC grants to AJS and MAG].

The role of texture in shape from shading: are humans biased towards seeing relief textures?

When a textured surface is modulated in depth and illuminated, the level of illumination varies across the surface, producing coarse-scale luminance modulations (LM) and amplitude modulation (AM) of the fine-scale texture. If the surface has an albedo texture (reflectance variation) then the LM and AM components are always in-phase, but if the surface has a relief texture the phase relation between LM and AM varies with the direction and nature of the illuminant. We showed observers sinusoidal luminance and amplitude modulations of a binary noise texture, in various phase relationships, in a paired-comparisons design. In the first experiment, the combinations under test were presented in different temporal intervals. Observers indicated which interval contained the more depthy stimulus. LM and AM in-phase were seen as more depthy than LM alone which was in turn more depthy than LM and AM in anti-phase, but the differences were weak. In the second experiment the combinations under test were presented in a single interval on opposite obliques of a plaid pattern. Observers were asked to indicate the more depthy oblique. Observers produced the same depth rankings as before, but now the effects were more robust and significant. Intermediate LM/AM phase relationships were also tested: phase differences less than 90 deg were seen as more depthy than LM-only, while those greater than 90 deg were seen as less depthy. We conjecture that the visual system construes phase offsets between LM and AM as indicating relief texture and thus perceives these combinations as depthy even when their phase relationship is other than zero. However, when different LM/AM pairs are combined in a plaid, the signals on the obliques are unlikely to indicate corrugations of the same texture, and in this case the out-of-phase pairing is seen as flat. [Supported by the Engineering and Physical Sciences Research Council (EPSRC)].

Development of a post-mitotic, neuronal-astrocytic cell system, for the prediction of acute neurotoxicity in humans

The human NT2.D1 cell line was differentiated to form both a 1:2 co-culture of post-mitotic NT2 neuronal and NT2 astrocytic (NT2.N/A) cells and a pure NT2.N culture. The respective sensitivities to several test chemicals of the NT2.N/A, the NT2.N, and the NT2.D1 cells were evaluated and compared with the CCF-STTG1 astrocytoma cell line, using a combination of basal cytotoxicity and biochemical endpoints. Using the MTT assay, the basal cytotoxicity data estimated the comparative toxicities of the test chemicals (chronic neurotoxin 2,5-hexanedione, cytotoxins 2,3- and 3,4-hexanedione and acute neurotoxins tributyltin- and trimethyltin- chloride) and also provided the non-cytotoxic concentration-range for each compound. Biochemical endpoints examined over the non-cytotoxic range included assays for ATP levels, oxidative status (H2O2 and GSH levels) and caspase-3 levels as an indicator of apoptosis. although the endpoints did not demonstrate the known neurotoxicants to be consistently more toxic to the cell systems with the greatest number of neuronal properties, the NT2 astrocytes appeared to contribute positively to NT2 neuronal health following exposure to all the test chemicals. The NT2.N/A co-culture generally maintained superior ATP and GSH levels and reduced H2O2 levels in comparison with the NT2.N mono-culture. In addition, the pure NT2.N culture showed a significantly lower level of caspase-3 activation compared with the co-culture, suggesting NT2 astrocytes may be important in modulating the mode of cell death following toxic insult. Overall, these studies provide evidence that an in vitro integrated population of post-mitotic human neurons and astrocytes may offer significant relevance to the human in vivo heterogeneous nervous system, when initially screening compounds for acute neurotoxic potential.

Humans:the missing link in manufacturing simulation?

Computer based discrete event simulation (DES) is one of the most commonly used aids for the design of automotive manufacturing systems. However, DES tools represent machines in extensive detail, while only representing workers as simple resources. This presents a problem when modelling systems with a highly manual work content, such as an assembly line. This paper describes research at Cranfield University, in collaboration with the Ford Motor Company, founded on the assumption that human variation is the cause of a large percentage of the disparity between simulation predictions and real world performance. The research aims to improve the accuracy and reliability of simulation prediction by including models of human factors.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.

Do simple intransitive finger movements consistently activate frontoparietal mirror neuron areas in humans?

The posterior inferior frontal gyrus (pIFG) and anterior inferior parietal lobule (aIPL) form the core regions of the human “mirror neuron system” that matches an observed movement onto its internal motor representation. We used event-related functional MRI to examine whether simple intransitive finger movements evoke “mirror activity” in the pIFG and aIPL. In separate sessions, participants either merely observed visuospatial stimuli or responded to them as quickly as possible with a spatially compatible finger movement. A picture of a relaxed hand with static dots on the tip of the index and little finger was continuously presented as high-level baseline. Four types of stimuli were presented in a pseudorandom order: a color change of a dot, a moving finger, a moving dot, or a simultaneous finger-dot movement. Dot movements were spatially and kinematically matched to finger movements. Participants were faster at imitating a finger movement than performing the same movement in response to a moving dot or a color change of a dot. Though imitative responses were facilitated, fMRI revealed no additional “mirror activity” in the pIFG and aIPL during the observation or imitation of finger movements as opposed to observing or responding to a moving dot. Mere observation of a finger movement alone failed to induce significant activation of the pIFG and aIPL. The lack of a signature of “mirror neuron activity” in the inferior frontoparietal cortex is presumably due to specific features of the task which may have favored stimulus–response mapping based on common spatial coding. We propose that the responsiveness of human frontoparietal mirror neuron areas to simple intransitive movements critically depends on the experimental context.

Modulation of long-range neural synchrony reflects temporal limitations of visual attention in humans

Because of attentional limitations, the human visual system can process for awareness and response only a fraction of the input received. Lesion and functional imaging studies have identified frontal, temporal, and parietal areas as playing a major role in the attentional control of visual processing, but very little is known about how these areas interact to form a dynamic attentional network. We hypothesized that the network communicates by means of neural phase synchronization, and we used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink). Our results reveal that communication within the fronto-parieto-temporal attentional network proceeds via transient long-range phase synchronization in the beta band. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioral performance. Thus, we show how attentional limitations arise from the way in which the subsystems of the attentional network interact. The human brain faces an inestimable task of reducing a potentially overloading amount of input into a manageable flow of information that reflects both the current needs of the organism and the external demands placed on it. This task is accomplished via a ubiquitous construct known as “attention,” whose mechanism, although well characterized behaviorally, is far from understood at the neurophysiological level. Whereas attempts to identify particular neural structures involved in the operation of attention have met with considerable success (1-5) and have resulted in the identification of frontal, parietal, and temporal regions, far less is known about the interaction among these structures in a way that can account for the task-dependent successes and failures of attention. The goal of the present research was, thus, to unravel the means by which the subsystems making up the human attentional network communicate and to relate the temporal dynamics of their communication to observed attentional limitations in humans. A prime candidate for communication among distributed systems in the human brain is neural synchronization (for review, see ref. 6). Indeed, a number of studies provide converging evidence that long-range interarea communication is related to synchronized oscillatory activity (refs. 7-14; for review, see ref. 15). To determine whether neural synchronization plays a role in attentional control, we placed humans in an attentionally demanding task and used magnetoencephalography (MEG) to track interarea communication by means of neural synchronization. In particular, we presented 10 healthy subjects with two visual target letters embedded in streams of 13 distractor letters, appearing at a rate of seven per second. The targets were separated in time by a single distractor. This condition leads to the “attentional blink” (AB), a well studied dual-task phenomenon showing the reduced ability to report the second of two targets when an interval <500 ms separates them (16-18). Importantly, the AB does not prevent perceptual processing of missed target stimuli but only their conscious report (19), demonstrating the attentional nature of this effect and making it a good candidate for the purpose of our investigation. Although numerous studies have investigated factors, e.g., stimulus and timing parameters, that manipulate the magnitude of a particular AB outcome, few have sought to characterize the neural state under which “standard” AB parameters produce an inability to report the second target on some trials but not others. We hypothesized that the different attentional states leading to different behavioral outcomes (second target reported correctly or not) are characterized by specific patterns of transient long-range synchronization between brain areas involved in target processing. Showing the hypothesized correspondence between states of neural synchronization and human behavior in an attentional task entails two demonstrations. First, it needs to be demonstrated that cortical areas that are suspected to be involved in visual-attention tasks, and the AB in particular, interact by means of neural synchronization. This demonstration is particularly important because previous brain-imaging studies (e.g., ref. 5) only showed that the respective areas are active within a rather large time window in the same task and not that they are concurrently active and actually create an interactive network. Second, it needs to be demonstrated that the pattern of neural synchronization is sensitive to the behavioral outcome; specifically, the ability to correctly identify the second of two rapidly succeeding visual targets

Acute mobile phone operation affects neural function in humans

OBJECTIVES: Mobile phones (MP) are used extensively and yet little is known about the effects they may have on human physiology. There have been conflicting reports regarding the relation between MP use and the electroencephalogram (EEG). The present study suggests that this conflict may be due to methodological differences such as exposure durations, and tests whether exposure to an active MP affects EEG as a function of time. METHODS: Twenty-four subjects participated in a single-blind fully counterbalanced cross-over design, where both resting EEG and phase-locked neural responses to auditory stimuli were measured while a MP was either operating or turned off. RESULTS: MP exposure altered resting EEG, decreasing 1-4 Hz activity (right hemisphere sites), and increasing 8-12 Hz activity as a function of exposure duration (midline posterior sites). MP exposure also altered early phase-locked neural responses, attenuating the normal response decrement over time in the 4-8 Hz band, decreasing the response in the 1230 Hz band globally and as a function of time, and increasing midline frontal and lateral posterior responses in the 30-45 Hz band. CONCLUSIONS: Active MPs affect neural function in humans and do so as a function of exposure duration. The temporal nature of this effect may contribute to the lack of consistent results reported in the literature.

Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans

Introduction. Peroxiredoxin (PRDX) and thioredoxin (TRX) are antioxidant proteins that control cellular signalling and redox balance, although their response to exercise is unknown. This study aimed to assess key aspects of the PRDX-TRX redox cycle in response to three different modes of exercise. Methods. Healthy males (n = 10, mean ± SD: 22 ± 3 yrs) undertook three exercise trials on separate days: two steady-state cycling trials at moderate (60% VO2MAX; 27 min, MOD) and high (80% VO2MAX; 20 min, HIGH) intensities, and a low-volume high-intensity interval training trial (10 × 1 min 90% VO2MAX, LV-HIIT). Peripheral blood mononuclear cells were assessed for TRX-1 and over-oxidised PRDX (isoforms I-IV) protein expression before, during, and 30 min following exercise (post + 30). The activities of TRX reductase (TRX-R) and the nuclear factor kappa B (NF-κB) p65 subunit were also assessed. Results. TRX-1 increased during exercise in all trials (MOD, + 84.5%; HIGH, + 64.1%; LV-HIIT, + 205.7%; p < 05), whereas over-oxidised PRDX increased during HIGH only (MOD, - 28.7%; HIGH, + 202.9%; LV-HIIT, - 22.7%; p < .05). TRX-R and NF-κB p65 activity increased during exercise in all trials, with the greatest response in TRX-R activity seen in HIGH (p < 0.05). Discussion. All trials stimulated a transient increase in TRX-1 protein expression during exercise. Only HIGH induced a transient over-oxidation of PRDX, alongside the greatest change in TRX-R activity. Future studies are needed to clarify the significance of heightened peroxide exposure during continuous high-intensity exercise and the mechanisms of PRDX-regulatory control.

Measurement of scleral thickness in humans using anterior segment optical coherent tomography

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-toposterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- And inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46μm. Meridian SN was the thinnest (662±57μm) and I the thickest (806 ±60μm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4mm. AST measurements at 1mm (682±48 μm) were the thinnest and at 6mm (818±49 μm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Health and population effects of rare gene knockouts in adult humans with related parents

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans.