Incorporation of 3,3'-Diindolylmethane into Nanocapsules Improves Its Photostability, Radical Scavenging Capacity, and Cytotoxicity Against Glioma Cells.

3,3'-Diindolylmethane (DIM) is a phytochemical that presents health benefits (antitumor, antioxidant, and anti-inflammatory effects). However, it is water insoluble and thermo- and photolabile, restraining its pharmaceutical applications. As a strategy to overcome such limitations, this study aimed the development and characterization of DIM-loaded nanocapsules (NCs) prepared with different compositions as well as the in vitro assessment of scavenging activity and cytotoxicity. The formulations were obtained using the interfacial deposition of preformed polymer method and were composed by Eudragit® RS100 or ethylcellulose as polymeric wall and primula or apricot oil as the core. All the formulations had adequate physicochemical characteristics: nanometric size (around 190 nm), low polydispersity index (< 0.2), pH value at acid range, high values of zeta potential, drug content, and encapsulation efficiency (~ 100%). Besides, nanoencapsulation protected DIM against UVC-induced degradation and increased the scavenging activity assessed by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) and 1-1-diphenyl-2-picrylhydrazyl methods. The developed DIM-loaded nanocapsules were further evaluated regarding the in vitro release profile and cytotoxicity against a human glioblastoma cell line (U87 cells). The results demonstrated that the nanoencapsulation promoted a sustained release of the bioactive compound (in the range of 58-78% after 84 h) in comparison to its free form (86% after 12 h), as well as provided a superior cytotoxic effect against the U87 cells in the highest concentrations. Therefore, our results suggest that nanoencapsulation could be a promising approach to overcome the DIM physicochemical limitations and potentialize its biological properties.

Cognitive neuroscience can support public health approaches to minimise the harm of 'losses disguised as wins' in multiline slot machines.

Video slot machines are associated with both accelerated transition into problematic forms of gambling, as well as psychosocial harm above and beyond other forms of gambling. A growing body of evidence is uncovering how key design features of multiline slot machines produce an inflated experience of reward, despite the fact that these features offer no overall financial benefit to the player. A pernicious example of this are 'losses disguised as wins' (LDWs), which occur when simultaneous bets placed on multiple lines result in a winning combination that returns an amount greater than zero, but less the total wager. These events are usually accompanied by the same celebratory sounds and animations that accompany true wins. We argue that LDWs may leverage neuropsychological phenomena that underlie reinforcement learning and contribute to extended or repetitive use and gambling-related harm. While other characteristics of slot machine gambling have been examined by cognitive neuroscientists, this feature has not yet received attention. Neuroscientific methods can be used to assess the impact of LDWs on the human reward system, to assess the claim that these events are a reinforcing and contributing factor in the development of harmful play. Positive findings would provide further persuasive evidence in support of strategies to minimise gambling harm through the regulation of machine design.

Current understanding of photophobia, visual networks and headaches.

OBJECTIVE: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders. BACKGROUND: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation. CONCLUSION: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Antioxidant effects of Lycium barbarum polysaccharides on photoreceptor degeneration in the light-exposed mouse retina.

We assessed the neuroprotective effects of Lycium barbarum Polysaccharides (LBP) on photoreceptor degeneration and the mechanisms involved in oxidative stress in light-exposed mouse retinas. Mice were given a gavage of LBP (150 mg/kg or 300 mg/kg) or phosphate buffered saline (PBS) for 7 days before exposure to light (5000 lx for 24 h). We found that LBP significantly improved the electroretinography (ERG) amplitudes of the a- and b-waves that had been attenuated by light exposure. In addition, changes caused by light exposure including photoreceptor cell loss, nuclear condensation, an increased number of mitochondria vacuoles, outer membrane disc swelling and cristae fractures were distinctly ameliorated by LBP. LBP treatment also significantly prevented the generation of reactive oxygen species (ROS) compared with PBS treatment. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase (TrxR1) mRNA were decreased in PBS-treated mice compared with controls but increased remarkably in LBP-treated mice. The mRNA levels of the DNA repair gene Poly (ADP-ribose) polymerase (PARP14) was increased in PBS-treated mice but decreased significantly in the LBP-treated mice. Our findings indicate that pretreatment with LBP effectively protected photoreceptor cells against light-induced retinal damage probably through the up-regulation of the antioxidative genes Nrf2 and TrxR1, the elimination of oxygen free radicals, and the subsequent reduction in the mitochondrial reaction to oxidative stress and enhancement in antioxidant capacity. In addition, the decreased level of PARP14 mRNA in LBP-treated mice also indicated a protective effect of LBP on delaying photoreceptor in the light-damaged retina.

Does emotion change auditory prediction and deviance detection?

In the last decades, a growing number of studies provided compelling evidence supporting the interplay of cognitive and affective processes. However, it remains to be clarified whether and how an emotional context affects the prediction and detection of change in unattended sensory events. In an event-related potential (ERP) study, we probed the modulatory role of pleasant, unpleasant and neutral visual contexts on the brain response to automatic detection of change in spectral (intensity) vs. temporal (duration) sound features. Twenty participants performed a passive auditory oddball task. Additionally, we tested the relationship between ERPs and self-reported mood. Participants reported more negative mood after the negative block. The P2 amplitude elicited by standards was increased in a positive context. Mismatch Negativity (MMN) amplitude was decreased in the negative relative to the neutral and positive contexts, and was associated with self-reported mood. These findings suggest that the detection of regularities in the auditory stream was facilitated in a positive context, whereas a negative visual context interfered with prediction error elicitation, through associated mood changes. Both ERP and behavioral effects highlight the intricate links between emotion, perception and cognitive processes.

[Possible Signs of Sensory Overload]. / Mögliche Kennzeichen der Reizüberflutung.

Objective To identify, synthesize and structure the defining characteristics of overstimulation. Methods The literature search was conducted in relevant international databases (Pubmed, Medline, CINAHL, Psyndex, PsycArticles, PsychINFO). The literature analysis was conducted according to Mayring's method of qualitative content analysis. Results Despite the scanty data available on symptoms or effects of sensory overload, twelve literature-sources were identified, describing signs and symptoms of sensory overload. A cluster of psychopathological and behavioral characteristics of sensory overload was developed. Conclusions Further research is needed to obtain an evidence-based description of the defining characteristics of sensory overload.

[Biological mechanisms of myopia]. / Biologische Mechanismen der Myopie.

Recent studies have confirmed that the prevalence of myopia has increased in most countries, that the increase must be due to environmental factors and that myopia is closely linked to the level of education. Extensive close-up work with short viewing distances, little outdoor activity and continuous exposure to low illumination are currently considered the major factors. It remains unknown how close-up work can stimulate eye growth. Animal models provide the possibility to manipulate visual experiences and to observe subsequent changes in eye growth. They have uncovered a number of unexpected aspects which have led to studies in children. When applied in low doses atropine (0.01 %) is effective against progression of myopia and shows no rebound effect after termination of the treatment, in contrast to treatment with previously used higher doses. While education cannot be limited in our society, there are now an increasing number of options to slow myopia progression so that high myopia is less frequently reached.

Alpha-range visual and auditory stimulation reduces the perception of pain.

BACKGROUND: Alpha power is believed to have an inverse relationship with the perception of pain. Increasing alpha power through an external stimulus may, therefore, induce an analgesic effect. Here, we attempt to modulate the perception of a moderately painful acute laser stimulus by separately entraining three frequencies across the alpha band: 8, 10 and 12 Hz. METHODS: Participants were exposed to either visual or auditory stimulation at three frequencies in the alpha-band range and a control frequency. We collected verbal pain ratings of laser stimuli from participants following 10 minutes of flashing LED goggle stimulation and 10 minutes of binaural beat stimulation across the alpha range. Alterations in sleepiness, anxiety and negative mood were recorded following each auditory or visual alpha-rhythm stimulation session. RESULTS: A significant reduction in pain ratings was found after both the visual and the auditory stimulation across all three frequencies compared with the control condition. In the visual group, a significantly larger reduction was recorded following the 10-Hz stimulation than succeeding the 8- and 12-Hz conditions. CONCLUSIONS: This study suggests that a short presentation of auditory and visual stimuli, oscillating in the alpha range, have an analgesic effect on acute laser pain, with the largest effect following the 10-Hz visual stimulation. Pain reductions following stimulation in the alpha range are independent of sleepiness, anxiety, and negative moods. SIGNIFICANCE: This study provides new behavioural evidence showing that visual and auditory entrainment of frequencies in the alpha-wave range can influence the perception of acute pain in humans.

Electrical stimulation of the amygdala modifies the negative feedback effect of glucocorticoids on the adrenocortical responses to stress.

OBJECTIVE: The amygdala (AMG) plays a facilitatory role in the hypothalamic-pituitary-adrenal (HPA) axis. The effect of the AMG on the negative feedback exerted by glucocorticoids (GC) is not clear. We investigated the effect of repeated electrical stimulation of the AMG on the feedback action of GC upon the adrenocortical (AC) response to stressful stimuli. METHODS: Rats received electrical stimulation into the central amygdalar nucleus once daily for 4 days. At days 5 and 12 after the onset of stimulation, rats were treated with dexamethasone (Dex) or vehicle and were exposed to either photic or acoustic stress stimuli, and serum corticosterone (CS) was measured. In another group of rats, we measured the binding of Dex to the hippocampal cytosol at 5 and 12 days after the AMG stimulation. RESULTS: At 5 and 12 days after the onset of stimulation or a sham control, stress increased the serum CS level. In the sham group, Dex completely inhibited the CS response, but at 5 days after stimulation, it was significantly less effective in doing this. At day 12, Dex was as effective as in the control group. AMG stimulation delayed the return of CS response to basal levels and caused a significant decrease in the binding capacity of Dex to hippocampal cytosol. CONCLUSION: Electrical stimulation of the AMG caused a transient impairment of the feedback action of GC upon the stress response. This effect may be due to the decrease in hippocampal corticosteroid receptors. This suggests that the impaired GC feedback caused by AMG stimulation may be involved in the facilitatory effect of the AMG on the function of the AC axis.

A plant-derived anti-nociceptive spray for reduction of pain with photodynamic therapy.

BACKGROUND: Photodynamic therapy is an effective tool in the management of some forms of skin cancer and generalized solar dermopathy and can be beneficial in the management of acne vulgaris. When used as an area treatment one of the main limiters is the quite severe burning pain that patients feel during the illumination phase of the treatment. OBJECTIVE: To examine the effectiveness of a plant derived anti-nociceptive spray applied prior to and during large area photodynamic therapy. METHODS: A split face or left arm versus right arm, placebo controlled trial was performed on 60 patients to assess the effectiveness of the spray in reducing pain perception. RESULTS: There was a statistically significant reduction in pain at all illumination points during the illumination phase but no significant difference in discomfort levels in the first 72 h post illumination. LIMITATIONS: Only large area photodynamic therapy treatment was performed during the study. No conclusions can be drawn for small area treatments. CONCLUSION: Use of a simple, plant derived anti-nociceptive spray can reduce the discomfort experienced by patients undergoing photodynamic therapy to large areas.

Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. METHODS: Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. RESULTS: Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. CONCLUSION: FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease.

Effect of mental fatigue caused by mobile 3D viewing on selective attention: an ERP study.

This study investigated behavioral responses to and auditory event-related potential (ERP) correlates of mental fatigue caused by mobile three-dimensional (3D) viewing. Twenty-six participants (14 women) performed a selective attention task in which they were asked to respond to the sounds presented at the attended side while ignoring sounds at the ignored side before and after mobile 3D viewing. Considering different individual susceptibilities to 3D, participants' subjective fatigue data were used to categorize them into two groups: fatigued and unfatigued. The amplitudes of d-ERP components were defined as differences in amplitudes between time-locked brain oscillations of the attended and ignored sounds, and these values were used to calculate the degree to which spatial selective attention was impaired by 3D mental fatigue. The fatigued group showed significantly longer response times after mobile 3D viewing compared to before the viewing. However, response accuracy did not significantly change between the two conditions, implying that the participants used a behavioral strategy to cope with their performance accuracy decrement by increasing their response times. No significant differences were observed for the unfatigued group. Analysis of covariance revealed group differences with significant and trends toward significant decreases in the d-P200 and d-late positive potential (LPP) amplitudes at the occipital electrodes of the fatigued and unfatigued groups. Our findings indicate that mentally fatigued participants did not effectively block out distractors in their information processing mechanism, providing support for the hypothesis that 3D mental fatigue impairs spatial selective attention and is characterized by changes in d-P200 and d-LPP amplitudes.

Rutin improves functional outcome via reducing the elevated matrix metalloproteinase-9 level in a photothrombotic focal ischemic model of rats.

BACKGROUND: Blood-brain barrier (BBB) disruption mediated by proteases plays a pivotal role in neural tissue damage after acute ischemic stroke. In an animal stroke model, the activation of matrix metalloproteinases (MMPs), especially MMP-9, was significantly increased and it showed potential association with blood-brain barrier (BBB) disruption and cerebral edema. Theoretically, it is expected that early blockade of expression and activation of MMP-9 after ischemic stroke provides neuroprotective effects from secondary neural tissue damage. This study was aimed to determine the ability of rutin to influence MMP-9 expression, activity and BBB disruption using a photothrombotic focal ischemic model in rats. METHODS: Adult male Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal cerebral ischemia by photothrombosis using Rose Bengal (RB) and cold light. Injured animals were divided into two groups; one group received 50mg/kg of rutin intraperitoneally, starting 1h after injury and at 12h intervals for 3 days, while animals in the control group received weight-adjusted doses of saline vehicle over the same period. In each group, the expressions and activities of MMP-9 were assessed by Western blot and gelatin zymography at 6, 24, 48, and 72 h after photothrombotic insult. The effects of rutin on BBB disruption and functional outcomes were also determined. RESULTS: Western blot and zymographic analysis showed up-regulated MMP-9 expression and activity in the ischemic cortex. The expression and activity of MMP-9 were significantly elevated at 6h after photothrombotic insult, which remained up-regulated for at least until 72 h after injury. In the rutin-treated group, MMP-9 expression and activity were significantly attenuated at 6, 24, and 48 h compared to the control group. Relative to the control group, BBB permeability was significantly reduced in the rutin-treated group. The results of the rotarod test revealed that rutin treatment significantly improved functional outcomes. CONCLUSIONS: Rutin treatment starting 1h after injury attenuated BBB disruption during photothrombotic focal ischemia, which was partly, at least, achieved through inhibitory effects on MMP-9 expression and activity. The results of this study suggest that rutin might be useful in clinical trials aimed to improve the outcome of patients suffering from acute ischemic stroke.

Is it dangerous to fantasize revenge in imagery exercises? An experimental study.

BACKGROUND: Imagery rescripting (ImRS), i.e. changing intrusive mental images in imagery, is increasingly recognized as a helpful therapy technique. In ImRS exercises, patients sometimes suggest taking violent revenge on perpetrators. However, it is unclear whether vengeful phantasies can be particularly helpful in giving back feelings of power and control, or whether they rather increase aggressive feelings, with potentially harmful effects. METHODS: Forty-six healthy participants watched 3 trauma movie segments depicting interpersonal violence. After each movie, one of 3 ImRS strategies (ImRS with violent revenge, ImRS without violence, safe place imagery) was applied. Dependent variables were subjective emotion ratings. RESULTS: Aggressive and positive emotions changed most strongly with the safe place image, no differences between ImRS with and without violence were observed. Sad and anxious emotions were not differently influenced by different strategies. LIMITATIONS: Only a healthy sample with no previous display of aggression has been investigated. Cross-over effects cannot be excluded due to the within-group design with repeated trauma movie segments. CONCLUSIONS: Using violent pictures in ImRS does not seem to be particularly risky as it does not increase aggressive emotions in the participants; however it has no added value. For the purpose of emotion regulation after an analog trauma, the safe place imagery does best.

Learned together, extinguished apart: reducing fear to complex stimuli.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuates fear responding and prevents the return of fear in pure tone Pavlovian fear conditioning. Here we sought to examine whether this effect also applies to a more complex fear memory. First, we show that after fear conditioning to the simultaneous presentation of a tone and a light (T+L) coterminating with a shock, the compound memory that ensues is more resistant to fear extinction than simple tone-shock pairings. Next, we demonstrate that the compound memory can be disrupted by interrupting the reconsolidation of the two individual components using a sequential retrieval+extinction paradigm, provided the stronger compound component is retrieved first. These findings provide insight into how compound memories are encoded, and could have important implications for PTSD treatment.

Seizure semiology in autosomal dominant epilepsy with auditory features, due to novel LGI1 mutations.

Mutations in LGI1 are found in 50% of families with autosomal dominant epilepsy with auditory features (ADEAF). In ADEAF, family members have predominantly lateral temporal lobe seizures but mesial temporal lobe semiology may also occur. We report here three families with novel LGI1 mutations (p.Ile82Thr, p.Glu225*, c.432-2_436del). Seven affected individuals reported an auditory aura and one a visual aura. A 10-year old boy described a cephalic aura followed by an unpleasant taste and oral automatisms without auditory, visual or psychic features.

White matter microstructural changes of thalamocortical networks in photosensitivity and idiopathic generalized epilepsy.

PURPOSE: Photosensitivity or photoparoxysmal response (PPR) is an electroencephalography trait that is highly associated with idiopathic generalized epilepsies (IGEs) and characterized by changes in cortical excitability in response to photic stimulation. Studying functional and structural changes of PPR might provide important insights into the pathogenesis of IGE. Recent studies revealed a functional network consisting of occipital, parietal, and precentral areas that might be implicated in PPR. Herein, we investigate the microstructural changes associated with PPR. METHODS: Twelve healthy subjects with PPR, nine patients with IGE and PPR (IGE-PPR group), and 18 healthy controls were studied with diffusion magnetic resonance imaging. Tract-based spatial statistics were used to test for regional differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity between groups. KEY FINDINGS: Subjects with PPR exhibited higher FA in the right precentral juxtacortical white matter and higher MD in lateral occipital areas relative to controls. Patients with IGE-patients showed additional increases in regional FA in the thalamus and juxtacortical precentral and parietal areas. Both subjects with PPR and patients with IGE-PPR presented axial and radial diffusivity changes in the occipital regions. SIGNIFICANCE: Our results show that PPR is associated with subcortical microstructural changes in precentral, parietal, and occipital regions. The coexistence of PPR and IGE is associated with white matter abnormalities in the thalamus and precuneus. PPR and epilepsy share similar functional and structural networks in widespread cortical and subcortical areas.

Reduced intrusion development after post-trauma imagery rescripting; an experimental study.

BACKGROUND AND OBJECTIVES: Contemporary theories predict PTSD development after trauma if trauma information is not adequately processed or negatively appraised. Mental imagery and emotional processing seem to be strongly related and evidence-based treatment strategies such as imaginal exposure and EMDR indeed include imagery as a main component. Moreover, imagery rescripting of traumatic memories is an effective treatment for PTSD. METHODS: The present study combined these lines of research and investigated the impact of early imagery rescripting on intrusion development after an aversive film. Seventy-six participants were randomly allocated to one of three conditions: imagery rescripting (IRS), imagery reexperiencing (IRE) and positive imagery (PI). All participants watched an aversive film, had a 30-min break and then received a 9-min intervention (IRS, IRE or PI). They indicated subjective distress during the intervention, recorded intrusive memories of the film for 1 week and completed the Posttraumatic Cognitions Inventory (PTCI) and a cued recall test one week later. RESULTS: The IRS group developed fewer intrusive memories relative to the IRE and PI groups, and less negative cognitions than the IRE group, while cued recall was enhanced in IRS and IRE groups compared to the PI group. IRS and PI groups experienced less distress during the intervention than the IRE group. LIMITATIONS: This is an analogue design and results should be replicated in clinical samples. CONCLUSIONS: The results suggest that IRS might be an adequate technique to change memory consolidation at an early stage and therefore a powerful and non-distressing strategy to prevent PTSD symptoms.

Imagery in the aftermath of viewing a traumatic film: using cognitive tasks to modulate the development of involuntary memory.

BACKGROUND AND OBJECTIVES: Involuntary autobiographical memories that spring unbidden into conscious awareness form part of everyday experience. In psychopathology, involuntary memories can be associated with significant distress. However, the cognitive mechanisms associated with the development of involuntary memories require further investigation and understanding. Since involuntary autobiographical memories are image-based, we tested predictions that visuospatial (but not other) established cognitive tasks could disrupt their consolidation when completed post-encoding. METHODS: In Experiment 1, participants watched a stressful film then immediately completed a visuospatial task (complex pattern tapping), a control-task (verbal task) or no-task. Involuntary memories of the film were recorded for 1-week. In Experiment 2, the cognitive tasks were administered 30-min post-film. RESULTS: Compared to both control and no-task conditions, completing a visuospatial task post-film reduced the frequency of later involuntary memories (Expts 1 and 2) but did not affect voluntary memory performance on a recognition task (Expt 2). LIMITATIONS: Voluntary memory was assessed using a verbal recognition task and a broader range of memory tasks could be used. The relative difficulty of the cognitive tasks used was not directly established. CONCLUSIONS: An established visuospatial task after encoding of a stressful experience selectively interferes with sensory-perceptual information processing and may therefore prevent the development of involuntary autobiographical memories.

Wide-dynamic-range APS-based silicon retina with brightness constancy.

A silicon retina is an intelligent vision sensor that can execute real-time image preprocessing by using a parallel analog circuit that mimics the structure of the neuronal circuits in the vertebrate retina. For enhancing the sensor's robustness to changes in illumination in a practical environment, we have designed and fabricated a silicon retina on the basis of a computational model of brightness constancy. The chip has a wide-dynamic-range and shows a constant response against changes in the illumination intensity. The photosensor in the present chip approximates logarithmic illumination-to-voltage transfer characteristics as a result of the application of a time-modulated reset voltage technique. Two types of image processing, namely, Laplacian-Gaussian-like spatial filtering and computing the frame difference, are carried out by using resistive networks and sample/hold circuits in the chip. As a result of these processings, the chip exhibits brightness constancy over a wide range of illumination. The chip is fabricated by using the 0.25- µm complementary metal-oxide semiconductor image sensor technology. The number of pixels is 64 × 64, and the power consumption is 32 mW at the frame rate of 30 fps. We show that our chip not only has a wide-dynamic-range but also shows a constant response to the changes in illumination.