Current Stimulus Research Articles

Improving Electrical Stimulation Effectiveness and Versatility for Non-Invasive Transdermal Monitoring Applications via an Innovative Mixed-Signal Electronic Interface

Electrical stimulation can be used in several applications such as fatigue reduction, muscle rehabilitation, neurorehabilitation, neuro-prosthesis and pain relief. Moreover, electrical stimulation can be used for drug delivery applications or body fluids extraction (e.g., sweat and interstitial fluid) to successively monitor several parameters, such as glucose, lactate, etc. All these applications are performed using electrical stimulator devices capable of applying constant voltage pulses or constant current pulses via electrodes to human tissues. Usually, constant current stimulators are most widely used because of their safety, stability, and repeatability. Thus, the aim of this work was to design, realize and test a mixed-signal electronic interface capable of producing current pulses with custom amplitude, duration, frequency, polarity and symmetry with extended voltage compliance. To achieve this result, we developed a high-voltage current stimulator suitable for iontophoresis applications. Current stimuli can be applied setting the intensity, frequency and duty cycle of the stimulation patterns through a µC. A custom electronic interface was designed to allow the control of the injected current in real time and to prevent electrical injuries to the patient by avoiding potential unwanted short circuits. Moreover, the system was tested in a simulated environment demonstrating its effectiveness and applicability for transdermal monitoring applications. The obtained results show that the device is able to apply monophasic and biphasic pulses, ranging from 0.1 to 10 mA, with a maximum error of about 10% at the minimum intensity; in addition, current stimuli can be applied up to a maximum frequency of 100 kHz with a voltage compliance of 120 V.

Ion‐Permeable Electrospun Scaffolds Enable Controlled In‐Vitro Electrostimulation Assay of Myoblasts

AbstractIn‐vitro models are fundamental for studying muscular cell contractility and for wide‐screening of therapeutic candidates targeting skeletal muscle diseases, owing to their scalability, reproducibility, and circumvention of ethical concerns. However, in‐vitro assays permitting reliable electrical stimulation of cell contractile activity still require technological development. Here, a novel approach to electrically stimulate differentiated muscular cell contractility is reported exploiting the ionic conductivity and mechanical flexibility of 3D nanofibrous scaffolds. The electrospun poly(L‐lactide‐co‐caprolactone) scaffold allowed for C2C12 murine myoblasts horizontal elongation and myotubes formation. Scaffold porosity enables high ionic conductivity and strong electric field generation, orthogonally oriented to the scaffold surface. Electrically induced cell contractility is determined with atomic force microscopy (AFM) enabling real‐time monitoring of scaffold vibrations in liquid environment. Differentiated cell actuation is found to be linearly correlated to current amplitude and number of current stimuli. Integrating the 3D nanofibrous scaffolds with real‐time AFM monitoring provides highly accurate in‐vitro assays for biomedical research. The induction of electric fields orthogonal to the scaffold surface allows for accurately mimicking the excitation‐contraction coupling mechanism observed in native skeletal muscle tissue. This work paves the way for the quantitative study of muscular cell dynamic behavior and physiology, further evaluating therapy effectiveness for muscular pathologies.

Effect of Calcium on the Characteristics of Action Potential Under Different Electrical Stimuli

This study investigates the role of calcium ions in the release of action potentials by comparing two models based on the framework: the standard HH model and a HH + Ca model that incorporates calcium ion channels. Purkinje cells’ responses to four types of electrical current stimuli—constant direct current, step current, square wave current, and sine current—were simulated to analyze the impact of calcium on action potential characteristics. The results indicate that, under the constant direct current stimulation, the action potential firing frequency of both models increased with the escalating current intensity, while the delay time of the first action potential decreased. However, when the current intensity exceeded a specific threshold, the peak amplitude of the action potential gradually diminished. The HH + Ca model exhibited a longer delay in the first action potential compared to the HH model but maintained an action potential release under stronger currents. In response to the step current, both models showed an increased action potential frequency with a higher current, but the HH + Ca model generated subthreshold oscillations under weak currents. With the square wave current, the action potential frequency increased, though the HH + Ca model experienced suppression under high-frequency weak currents. Under the sine current, the action potential frequency rose, with the HH + Ca model showing less depression near the sine peak due to calcium’s role in modulating membrane potential. These findings suggest that calcium ions contribute to a more stable action potential release under varying stimuli.

Bistable Perception Discriminates Between Depressive Patients, Controls, Schizophrenia Patients, and Their Siblings.

Individuals with schizophrenia have less priors than controls, meaning they rely less upon their prior experiences to interpret the current stimuli. These differences in priors are expected to show as higher alternation rates in bistable perception tasks like the Structure-from-Motion (SfM) paradigm. In this paradigm, continuously moving dots in two dimensions are perceived subjectively as traveling along a three-dimensional sphere, which results in a direction of motion (left or right) that shifts approximately every few seconds. Here, we tested healthy controls, patients with schizophrenia, siblings of patients with schizophrenia, and patients with depression with both the intermittent and continuous variants of the SfM paradigm. In the intermittent variant of the SfM paradigm, depressive patients exhibited the lowest alternation rate, followed by unaffected controls. In contrast, patients with schizophrenia and their unaffected siblings displayed significantly higher alternation rates. In the continuous variant of the SfM paradigm, patients with schizophrenia showed the lowest mean percept durations, while there were no differences between the other three groups. The intermittent SfM paradigm is a candidate endophenotype for schizophrenia. The aberrant processing in the patients may stem from alterations in adaptation and/or cross-inhibition mechanisms leading to changes in priors, as suggested by current models in the field. The intermittent SfM paradigm is, hence, a trait marker that offers the great opportunity to investigate perceptual abnormalities across the psychiatry spectrum, ranging from depression to psychosis.

Dynamical effects of low-frequency and high-frequency current stimuli in a memristive Morris–Lecar neuron model

This paper deduces that the potassium and calcium ion currents in the two-dimensional (2D) Morris–Lecar neuron model can be respectively characterized by a passive memristor and a locally active memristor. Then a memristive Morris–Lecar neuron model with an equivalent circuit scheme is first constructed. The equilibrium trajectory and its stability are analyzed, which displays fold and Hopf bifurcations with proper model parameters. Bursting behavior and mixed-mode oscillations with after-depolarizing potential for low-frequency current stimulus are numerically disclosed. Besides, the bifurcation mechanisms for bursting behavior and mixed-mode oscillations are theoretically deduced. Furthermore, the firing patterns and antimonotonicity phenomenon for high-frequency current stimulus are numerically discovered. This study provides a new concept for building memristive bionic circuits from neuron models with well-defined ion channel currents.

Tribo-hygro-electric generator: Harnessing mechanical energy with liquid-infused porous cellulose for multiple sensing and DC power generation

This study introduces the Tribo-Hygro-Electric Generator (THEG), a novel device that harvests ambient mechanical and water-enabled energies for highly sensitive, self-powered multi-sensing. THEG employs a simple design using liquid-infused porous cellulose (LIPC), created by absorbing functional liquids such as water into porous cellulose, and metal contacts with distinct work functions (e.g., Al and Cu) to generate triboelectric charges through friction. It operates via a three-step process: generating triboelectric charges through sliding motion, establishing an internal electric field across Al/LIPC/Cu interfaces for charge separation, and directing charges to create unidirectional output electron transfer, producing direct current (DC) outputs. The principle behind THEG emphasizes the critical role of the single Schottky contact at the Al/LIPC interface in separating and directing charge transfer, as well as the conductive path formed by the hydrogen-bonded network of water molecules and cellulose’s functional groups. THEG can harvest DC power with a current density of up to 3.4 A/m² and 0.5 V, which can be increased to 2 V with four cells in series. THEG demonstrates impressive multiple-sensing capabilities, with robust linear relationships (correlation coefficients > 0.99) between output current density and stimuli such as pressure, velocity, water absorption, and ion concentration. Demonstrating practical utility, the generated energy powers devices like a commercial calculator. This technology advances mechanical energy harvesting and multiple sensing, reducing dependence on external power and enabling transformative IoT applications.

Serial dependencies for externally and self-generated stimuli.

Our senses are constantly exposed to external stimulation. Part of the sensory stimulation is produced by our own movement, like visual motion on the retina or tactile sensations from touch. Sensations caused by our movements appear attenuated. The interpretation of current stimuli is influenced by previous experiences, known as serial dependencies. Here we investigated how sensory attenuation and serial dependencies interact. In Experiment 1, we showed that temporal predictability causes sensory attenuation. In Experiment 2, we isolated temporal predictability in a visuospatial localization task. Attenuated stimuli are influenced by serial dependencies. However, the magnitude of the serial dependence effects varies, with greater effects when the certainty of the previous trial is equal to or greater than the current one. Experiment 3 examined sensory attenuation's influence on serial dependencies. Participants localized a briefly flashed stimulus after pressing a button (self-generated) or without pressing a button (externally generated). Stronger serial dependencies occurred in self-generated trials compared to externally generated ones when presented alternately but not when presented in blocks. We conclude that the relative uncertainty in stimulation between trials determines serial dependency strengths.

The tilt illusion arises from an efficient reallocation of neural coding resources at the contextual boundary.

The tilt illusion - a bias in the perceived orientation of a center stimulus induced by an oriented surround - illustrates how context shapes visual perception. While the tilt illusion has been the subject of quantitative study for over 85 years, we still lack a comprehensive account of the phenomenon that connects its neural and behavioral characteristics. Here, we demonstrate that the tilt illusion originates from a dynamic change in neural coding precision induced by the surround context. We simultaneously obtained psychophysical and fMRI responses from human subjects while they viewed gratings in the absence and presence of an oriented surround, and extracted sensory encoding precision from their behavioral and neural data. Both measures show that in the absence of a surround, encoding reflects the natural scene statistics of orientation. However, in the presence of an oriented surround, encoding precision is significantly increased for stimuli similar to the surround orientation. This local change in encoding is sufficient to accurately predict the behavioral characteristics of the tilt illusion using a Bayesian observer model. The effect of surround modulation increases along the ventral stream, and is localized to the portion of the visual cortex with receptive fields at the center-surround boundary. The pattern of change in coding accuracy reflects the surround-conditioned orientation statistics in natural scenes, but cannot be explained by local stimulus configuration. Our results suggest that the tilt illusion naturally emerges from a dynamic coding strategy that efficiently reallocates neural coding resources based on the current stimulus context.

Differential Anti-Inflammatory Effects of Electrostimulation in a Standardized Setting.

The therapeutic usage of physical stimuli is framed in a highly heterogeneous research area, with variable levels of maturity and of translatability into clinical application. In particular, electrostimulation is deeply studied for its application on the autonomous nervous system, but less is known about the anti- inflammatory effects of such stimuli beyond the inflammatory reflex. Further, reproducibility and meta-analyses are extremely challenging, owing to the limited rationale on dosage and experimental standardization. It is specifically to address the fundamental question on the anti-inflammatory effects of electricity on biological systems, that we propose a series of controlled experiments on the effects of direct and alternate current delivered on a standardized 3D bioconstruct constituted by fibroblasts and keratinocytes in a collagen matrix, in the presence or absence of TNF-α as conventional inflammation inducer. This selected but systematic exploration, with transcriptomics backed by metabolomics at specific time points allows to obtain the first systemic overview of the biological functions at stake, highlighting the differential anti-inflammatory potential of such approaches, with promising results for 5 V direct current stimuli, correlating with the wound healing process. With our results, we wish to set the base for a rigorous systematic approach to the problem, fundamental towards future elucidations of the detailed mechanisms at stake, highlighting both the healing and damaging potential of such approaches.

Characterizing serial dependence as an attraction to prior response.

Serial dependence refers to a common misperception that can occur between subsequently observed stimuli. Observers misreport the current stimulus as being more similar to the previous stimulus than it objectively is. It has been proposed that this bias may reflect an attraction of the current percept to prior percept (Fischer & Whitney, 2014). Alternatively, serial dependence has also been proposed to be the result of an assimilative effect between observer decisions (Fritsche, Mostert, & de Lange, 2017; Pascucci, Mancuso, Santandrea, Libera, Plomp, & Chelazzi, 2019). Lying within this debate is the issue of how we quantify serial dependence. Should this be as a bias induced by prior stimuli or by prior responses? We investigated this by manipulating the orientation of the current stimuli such that they fell between previous stimulus and previous response. We observed an attraction to previous response and a concomitant repulsion from previous stimulus. This suggests that the attractive effect of serial dependence in orientation judgments is best quantified in relation to prior response.

The impact of task measurements on sequential dependence: a comparison between temporal reproduction and discrimination tasks

Decisions about a current stimulus are influenced by previously encountered stimuli, leading to sequential bias. However, the specific processing levels at which serial dependence emerges remain unclear. Despite considerable evidence pointing to contributions from perceptual and post-perceptual processes, as well as response carryover effects impacting subsequent judgments, research into how different task measurements affect sequential dependencies is limited. To address this gap, the present study investigated the role of task type in shaping sequential effects in time perception, employing a random-dot kinematogram (RDK) in a post-cue paradigm. Participants had to remember both the duration and the direction of the RDK movement and perform the task based on a post-cue, which was equally likely to be direction or duration. To delineate the task type, we employed the temporal bisection task in Experiment 1 and the duration reproduction task in Experiment 2. Both experiments revealed a significant sequential bias: durations were perceived as longer following longer previous durations, and vice versa. Intriguingly, the sequential effect was enhanced in the reproduction task following the same reproduction task (Experiment 2), but did not show significant variation by the task type in the bisection task (Experiment 1). Moreover, comparable response carryover effects were observed across two experiments. We argue that the differential impacts of task types on sequential dependence lies in the involvement of memory reactivation process in the decision stage, while the post-decision response carryover effect may reflect the assimilation by subjective, rather than objective, durations, potentially linking to the sticky pacemaker rate and/or decisional inertia.

Dynamical behavior of memristive Hopfield neural network under pulsed current excitation

This paper investigates the effect of pulsed currents and multi-piecewise memristor on dynamic behavior of memristive Hopfield neural network (HNN). Firstly, a four-neuron HNN model is constructed by using the traditional memristor as the connecting synapse and its dynamic behavior is analyzed. Secondly, the traditional memristor in the HNN is replaced with a multi-piecewise memristor, and external pulse currents are applied to the model. The system exhibits rich dynamical behavior by introducing varying numbers of pulse current stimuli and adjusting the parameters of the multi-piecewise memristor. Experimental results demonstrate that the number of attractors in the system changes when pulse currents are applied, and after a period of chaotic behavior, the system eventually exhibits periodic activity. Furthermore, adjusting the parameters of the multi-piecewise memristor can generate multiple scroll attractors in the system. Finally, the experimental results were verified by Multisim.

Temporal asymmetry of neural representations predicts memory decisions.

A stimulus can be familiar for multiple reasons. It might have been recently encountered, or is similar to recent experience, or is similar to 'typical' experience. Understanding how the brain translates these sources of similarity into memory decisions is a fundamental, but challenging goal. Here, using fMRI, we computed neural similarity between a current stimulus and events from different temporal windows in the past and future (from seconds to days). We show that trial-by-trial memory decisions (is this stimulus 'old'?) were predicted by the difference in similarity to past vs. future events (temporal asymmetry). This relationship was (i) evident in lateral parietal and occipitotemporal cortices, (ii) strongest when considering events from the recent past (minutes ago), and (iii) most pronounced when veridical (true) memories were weak. These findings suggest a new perspective in which the brain supports memory decisions by comparing what actually occurred to what is likely to occur.

A Novel Coupled Memristive Izhikevich Neuron Model and Its Complex Dynamics

This paper proposes a novel, five-dimensional memristor synapse-coupled Izhikevich neuron model under electromagnetic induction. Firstly, we analyze the global exponential stability of the presented system by constructing an appropriate Lyapunov function. Furthermore, the Hamilton energy functions of the model and its corresponding error system are derived by using Helmholtz’s theorem. In addition, the influence of external current and system parameters on the dynamical behavior are investigated. The numerical simulation results indicate that the discharge pattern of excitatory and inhibitory neurons changes significantly when the amplitude and frequency of the external stimulus current are applied at different degrees. And the crucial dynamical behavior of the neuronal system is determined by the intensity of modulation of the induced current and the gain in the electromagnetic induction. Moreover, the amount of Hamilton energy released by the model could be evaluated during the conversion between the distinct dynamical behaviors.

Design and simulation of artificial retinal stimulation IC with switched capacitor using Si nanowire optical properties.

This study introduces an approach for converting the current from a sensor into controllable voltage. To this end, a switched-capacitor structure was integrated to provide efficient current-to-voltage conversion. The generated voltage was further regulated by an operational amplifier current source, enhancing stability and precision. An n-type metal oxide semiconductor field-effect transistor structure under an H-bridge was integrated into the system to achieve fine-tuned control over current stimulation. This component contributed to voltage regulation and enabled bi-directional control of current flow, offering versatility in adjusting current amplitudes using working and counter electrodes. This dynamic control mechanism was pivotal for effectively controlling the intensity of current stimulation. We applied Verilog-A modeling to simulate the optical characteristics of Si nanowires. The proposed system efficiently converted sensor-derived current into voltage using a switched-capacitor structure. Simultaneously, the precision was enhanced via operational amplifier regulation and n-type metal-oxide-semiconductor field-effect transistor-based H-bridge control. The simulation showed a current stimulus amplitude ranging from 2 to 13 μA for a variable photocurrent of Si nanowires (Rex: 10 kΩ, pulse: 100 Hz, 1 ms). The ability to finely control current stimulation intensity holds promise for diverse applications requiring accurate and adjustable current manipulation. This study contributes to the growing field of sensor technology by offering a unique perspective on the integration of nanostructures and electronic components for an enhanced control and functionality.

In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity.

Enhanced electrical activity in detrusor smooth muscle (DSM) cells is a key factor in detrusor overactivity which causes overactive bladder pathological disorders. Transient receptor potential melastatin-4 (TRPM4) channels, which are calcium-activated cation channels, play a role in regulating DSM electrical activities. These channels likely contribute to depolarizing the DSM cell membrane, leading to bladder overactivity. Our research focuses on understanding TRPM4 channel function in the DSM cells of mice, using computational modeling. We aimed to create a detailed computational model of the TRPM4 channel based on existing electrophysiological data. We employed a modified Hodgkin-Huxley model with an incorporated TRP-like current to simulate action potential firing in response to current and synaptic stimulus inputs. Validation against experimental data showed close agreement with our simulations. Our model is the first to analyze the TRPM4 channel's role in DSM electrical activity, potentially revealing insights into bladder overactivity. In conclusion, TRPM4 channels are pivotal in regulating human DSM function, and TRPM4 channel inhibitors could be promising targets for treating overactive bladder.

To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

Context-specific adaptation for head fakes in basketball: a study on player-specific fake-frequency schedules.

In basketball, an attacking player often plays a pass to one side while looking to the other side. This head fake provokes a conflict in the observing opponent, as the processing of the head orientation interferes with the processing of the pass direction. Accordingly, responses to passes with head fakes are slower and result in more errors than responses to passes without head fakes (head-fake effect). The head-fake effect and structurally similar interference effects (e.g., Stroop effect) are modulated by the frequency of conflicting trials. Previous studies mostly applied a block-wise manipulation of proportion congruency. However, in basketball (and also in other team sports), where different individual opponents can be encountered, it might be important to take the individual frequency (e.g., 20% vs. 80%) of these opponents into account. Therefore, the present study investigates the possibility to quickly (i.e., on a trial-by-trial basis) reconfigure the response behavior to different proportions of incongruent trials, which are contingent on different basketball players. Results point out that participants indeed adapted to the fake-frequency of different basketball players, which could be the result of strategic adaptation processes. Multi-level analyses, however, indicate that a substantial portion of the player-specific adaptation to fake frequencies is accounted by episodic retrieval processes, suggesting that item-specific proportion congruency effects can be explained in terms of stimulus-response binding and retrieval: The head orientation (e.g., to the right) of a current stimulus retrieves the last episode with the same head orientation including the response that was part of this last episode. Thus, from a theoretical perspective, an attacking player would provoke the strongest detrimental effect on an opponent if s/he repeats the same head movement but changes the direction of the pass. Whether it is at all possible to strategically apply this recommendation in practice needs still to be answered.

Effects of Acute Hypernatremia on the Electrophysiology of Single Human Ventricular Cardiomyocytes: An In Silico Study.

Clinical and experimental data on the cardiac effects of acute hypernatremia are scarce and inconsistent. We aimed to determine and understand the effects of different levels of acute hypernatremia on the human ventricular action potential. We performed computer simulations using two different, very comprehensive models of the electrical activity of a single human ventricular cardiomyocyte, i.e., the Tomek-Rodriguez model following the O'Hara-Rudy dynamic (ORd) model and the Bartolucci-Passini-Severi model as published in 2020 (known as the ToR-ORd and BPS2020 models, respectively). Mild to extreme levels of hypernatremia were introduced into each model based on experimental data on the effects of hypernatremia on cell volume and individual ion currents. In both models, we observed an increase in the intracellular sodium and potassium concentrations, an increase in the peak amplitude of the intracellular calcium concentration, a hyperpolarization of the resting membrane potential, a prolongation of the action potential, an increase in the maximum upstroke velocity, and an increase in the threshold stimulus current at all levels of hypernatremia and all stimulus rates tested. The magnitude of all of these effects was relatively small in the case of mild to severe hypernatremia but substantial in the case of extreme hypernatremia. The effects on the action potential were related to an increase in the sodium-potassium pump current, an increase in the sodium-calcium exchange current, a decrease in the rapid and slow delayed rectifier potassium currents, and an increase in the fast and late sodium currents. The effects of mild to severe hypernatremia on the electrical activity of human ventricular cardiomyocytes are relatively small. In the case of extreme hypernatremia, the effects are more pronounced, especially regarding the increase in threshold stimulus current.

Eye movements reflect active statistical learning.

What is the link between eye movements and sensory learning? Although some theories have argued for an automatic interaction between what we know and where we look that continuously modulates human information gathering behavior during both implicit and explicit learning, there exists limited experimental evidence supporting such an ongoing interplay. To address this issue, we used a visual statistical learning paradigm combined with a gaze-contingent stimulus presentation and manipulated the explicitness of the task to explore how learning and eye movements interact. During both implicit exploration and explicit visual learning of unknown composite visual scenes, spatial eye movement patterns systematically and gradually changed in accordance with the underlying statistical structure of the scenes. Moreover, the degree of change was directly correlated with the amount and type of knowledge the observers acquired. This suggests that eye movements are potential indicators of active learning, a process where long-term knowledge, current visual stimuli and an inherent tendency to reduce uncertainty about the visual environment jointly determine where we look.