Influence of indeloxazine hydrochloride upon photic driving responses elicited by flickering dot pattern and red flicker stimuli in elderly patients

We studied the influence of indeloxazine hydrochloride (IH) upon photic driving responses (PDRs) elicited by a 5 Hz flickering dot pattern and red flicker stimuli. Comparisons were made from a total of 22 elderly patients. By oral IH administration, clinical improvement was found in 12 patients with cerebral arteriosclerosis (improved group), whereas it was not observed in 6 patients with cerebral arteriosclerosis, 2 patients with multiinfarct dementia and 2 patients with Alzheimer's disease (unimproved group). Before and after the IH administration, an EEG examination by the above visual stimuli was carried out in each patient; a power spectral analysis of the occipital PDRs elicited by the visual stimuli was then made. The powers of PDRs elicited by the flickering dot pattern stimulation were not significantly different in both groups; those of 10 and 15 Hz PDRs elicited by the red flicker stimulation, however, decreased significantly by the IH administration in the improved group. It was suggested that such an analysis of PDRs elicited by the red flicker stimulation might perhaps be useful as one of the indicators to evaluate the efficacy of IH.     

Usefulness of Blue Sunglasses in Photosensitive Epilepsy

The suppressive effect of sunglasses upon photoparoxysmal responses (PPRs) elicited by 15-Hz flicker stimuli with a low luminance of nearly 10 nits was studied in eight patients with photosensitive epilepsy. Using three commercially available sunglasses of neutral density (ND), blue, and brown, the influence upon generalized PPRs elicited by a flickering dot pattern (FDP) and red flicker (RF) stimuli was separately examined in six patients; the luminance of the visual stimuli decreased from roughly one-fifth (ND and brown sunglasses) to one-tenth (blue sunglasses). With FDP stimulation, four of the six patients wearing each of the three sunglasses had no provocation of PPRs, whereas two of the six patients had provocation of generalized PPRs with all of the sunglasses. With RF stimulation, two of the six patients wearing ND sunglasses had provocation of generalized PPRs; three of the six patients wearing brown sunglasses had similar provocation; in contrast, none of the six patients showed provocation of PPRs while wearing blue sunglasses. These results suggest that the suppressive effect of the three sunglasses on FDP stimulation is mainly due to a luminance diminution, whereas that of blue sunglasses on RF stimulation is produced by an inhibitory effect of short wavelengths and possibly by a luminance diminution. Thus, blue sunglasses are thought to be useful in the treatment of patients with photosensitive epilepsy.     

A new adaptive temporal filter: application to photosensitive seizure patients

A new adaptive temporal filtering (ATF) technique was developed to prevent heath hazards due to flicker stimuli from televisions, videos or other displays. This ATF method could reduce frame-to-frame or field-to-field flicker stimuli at around 10-30 Hz which are particularly risky for photosensitive individuals. The present ATF efficacy with a computer simulation was studied in 11 photosensitive epilepsy patients. In order to control visual stimuli and induce photoparoxysmal response (PPR), we employed a problematic scene of the Pocket Monster incident containing 12 Hz red/blue flicker images lasting for 4 s. This image, shown with a 14-inch, television set 2 m in front of subjects, promptly elicited generalized PPR in all cases, while the filtered image did not induce any PPR. These results suggest that the present ATF method may be useful as a preventive measure of photosensitive seizures triggered by stimulative images from televisions or other displays.     

Photic driving evoked by hemifield flickering dot pattern stimulation in a patient with brain tumor

We have described photic driving evoked by hemifield 5/sec flickering dot pattern stimulation in a patient suffering from a metastatic tumor in the left parietal lobe. Based on an analysis of the photic driving in this particular patient, the left upper lip of the visual cortex is presumed to be the most sensitive to 5/sec flickering dot pattern stimulation. It is suggested that such an examination might be useful for determining local functional disturbance in the visual cortex.     

Photoparoxysmal response elicited by flickering dot pattern stimulation to the center and periphery.

OBJECTIVE: We performed this study to elucidate the roles of stimulus spatial frequency and visual field in eliciting generalized photoparoxysmal response (PPR) by flickering dot pattern (FDP) stimulation. METHODS: We studied 20 photosensitive epilepsy patients, aged 7-48 years (means +/- SD, 21.4+/-11.7 years), producing a 20 Hz FDP stimulation with a strobo-filter. Using dot patterns (0.5, 1, 2, 4 and 6 mm in diameter), we gave FDP stimulation to the center (11x11 degrees ) and periphery (11-30x11-30 degrees ) of subjects with eyes open, and analyzed each PPR appearance latency. RESULTS: Significant results were: latency by 1 (2.1 c/deg) and 0.5 mm (4.9 c/deg) FDP stimulation to the center was shorter than that to the periphery; latency by 4 mm (0.8 c/deg) FDP stimulation to the periphery was shorter than that to the center. As for 2 (1.5 c/deg) and 6 mm (0.5 c/deg) FDP stimuli, no significant difference could be observed. CONCLUSIONS: A higher spatial frequency FDP stimulation to the center elicits PPR more strongly than that to the periphery, whereas a lower spatial frequency FDP stimulation showed the opposite result, with peripheral stimulation being more effective than central stimulation.     

Concurrent recording of steady-state and transient event-related potentials as indices of visual-spatial selective attention.

OBJECTIVES: The present study investigated the effects of spatial attention on concurrently recorded visual event-related potentials (ERPs) and steady-state visual evoked potentials (SSVEPs) to isoluminant color changes embedded in rapidly flickering stimuli. METHODS: EEG was recorded while subjects attended to flickering LEDs in either the right or left visual hemifield and responded by a button press to isoluminant color changes (targets). RESULTS: Target isoluminant color changes elicited the typical ERP components P1, N1, N2 and P3, which were enhanced for attended targets compared to unattended targets. Consistent with previous findings, SSVEP amplitude was enlarged for attended flicker stimuli at posterior electrode sites contralateral to the attended visual hemifield. In addition, significant correlations were found between the N1, N2 and the SSVEP attention effects, whereas no such correlations were found between the P1, P3 and SSVEP attention effects. CONCLUSIONS: Results suggest that the SSVEP and ERP reflect partially overlapping attentional mechanisms that facilitate the discriminative processing of stimuli at attended locations.     

Combining steady-state visual evoked potentials and f MRI to localize brain activity during selective attention

Brain activity was studied with fMRI and steady-state visual evoked potentials (SSVEPs) in separate sessions as subjects attended to letter sequences in either the right or left visual field. The two letter sequences were superimposed on small square backgrounds that flickered at 8.6 and 12.0 Hz, respectively, and elicited SSVEPs at the flicker frequencies. The amplitude of the frequency-coded SSVEP elicited by either of the flickering backgrounds was enlarged when attention was focused upon the letter sequence at the same location. Source analysis of the SSVEP waveforms localized the attentional modulation to ventral and lateral extrastriate visual cortex, which corresponded to zones of activation observed with fMRI. Hum. Brain Mapping 5:287–292, 1997. © 1997 Wiley-Liss, Inc.     

Two Visual Mechanisms of Photosensitivity

PURPOSE: Photosensitive epilepsy is the most common of the "reflex" epilepsies. Precipitated by television viewing, flickering light, or specific visual patterns, it is the cause of seizures in 10% of young people with epilepsy. Photosensitivity is associated with two types of EEG abnormalities: photoparoxysmal responses (PPRs) and occipital spikes (OSs). It is unclear whether these abnormalities are mediated by different mechanisms, and furthermore, the clinical significance of OS is unknown. METHODS: By using our previously established population of patients with photosensitive epilepsy, all showing EEG abnormalities on intermittent photic stimulation or pattern stimulation, we examined the effects of pattern contrast, spatial and counterphase temporal frequency, and colour on these abnormalities. RESULTS: PPRs and not OSs show linear contrast dependency and are elicited by stationary stimuli and by non-colour-opponent isoluminant stimuli. CONCLUSIONS: PPRs and OSs are generated independently by the parvocellular and magnocellular visual systems, respectively. The results add support to the hypothesis that only PPRs and not OSs are clinically significant.     

tACS phase-specifically biases brightness perception of flickering light

BackgroundVisual phenomena like brightness illusions impressively demonstrate the highly constructive nature of perception. In addition to physical illumination, the subjective experience of brightness is related to temporal neural dynamics in visual cortex.ObjectiveHere, we asked whether biasing the temporal pattern of neural excitability in visual cortex by transcranial alternating current stimulation (tACS) modulates brightness perception of concurrent rhythmic visual stimuli.MethodsParticipants performed a brightness discrimination task of two flickering lights, one of which was targeted by same-frequency electrical stimulation at varying phase shifts. tACS was applied with an occipital and a periorbital active control montage, based on simulations of electrical currents using finite element head models.ResultsExperimental results reveal that flicker brightness perception is modulated dependent on the phase shift between sensory and electrical stimulation, solely under occipital tACS. Phase-specific modulatory effects by tACS were dependent on flicker-evoked neural phase stability at the tACS-targeted frequency, recorded prior to electrical stimulation. Further, the optimal timing of tACS application leading to enhanced brightness perception was correlated with the neural phase delay of the cortical flicker response.ConclusionsOur results corroborate the role of temporally coordinated neural activity in visual cortex for brightness perception of rhythmic visual input in humans. Phase-specific behavioral modulations by tACS emphasize its efficacy to transfer perceptually relevant temporal information to the cortex. These findings provide an important step towards understanding the basis of visual perception and further confirm electrical stimulation as a tool for advancing controlled modulations of neural activity and related behavior.     

Abnormal visual adaptation to flicker in multiple sclerosis

A visual psychophysical adaptation procedure was used on patients with Multiple Sclerosis (MS) in an attempt to induce a temporary and local exacerbation of subclinical visual impairment. Using a flicker detection task, sensitivity before and after adaptation to a flickering stimulus was measured in 9 MS patients and 9 control subjects. Although only 22% of patient eyes had abnormal flicker sensitivity prior to adaptation, visual deficit was observed in 83% of eyes studied after adaptation. Of the 7 MS eyes studied for which no other sign or symptom of visual involvement was present, 5 were found to have visual deficits after flicker adaptation. In addition, 10 of the 11 eyes affected by MS showed an abnormal response to flicker adaptation. Recovery from the effects of adaptation was complete in all patients within 2 minutes. The results suggest that partial demyelination of visual pathway neurons may exist in patients without signs or symptoms of visual involvement. The prolonged stimulation provided during adaptation may produce a temporary fatiguing or conduction blockade of such neurons which may lead to reductions in sensory sensitivity.     

A differential color flicker test for detecting acquired color vision impairment in multiple sclerosis and diabetic retinopathy

BackgroundOptic neuritis related to multiple sclerosis and diabetic retinopathy are relatively selective post-retinal and retinal vision disorders. Vision impairment in both conditions is reliably measured by testing critical fusion frequency (CFF).MethodsTo examine color vision, we measured the CFF in response to red and blue stimuli, and tested CFF values in patients without evident vision impairment. To ensure that differences in CFF values in a given subject depended only on color perception we displayed red and blue flickering stimuli at equal luminance. CFF to red or blue stimuli were compared in patients with medical history of optic neuritis related to multiple sclerosis (post-retinal vision impairment), patients with diabetic retinopathy (retinal vision impairment) and healthy subjects.ResultsThe test procedure disclosed altered CFF values for red and blue stimuli in both groups of patients studied. The comparison between the two groups disclosed a prevalent CFF impairment for red stimuli in patients with optic neuritis related to multiple sclerosis and for blue stimuli in patients with diabetic retinopathy.ConclusionsThe differential color flicker test appears highly accurate in detecting color vision impairment. Comparison of the two color CFFs differentiates retinal from post-retinal visual disorders.     

Steady-state visual evoked potentials during migraine prophylaxis by propranolol and femoxetine

ABSTRACT— The amplitude of visual evoked potentials (VEPs) for flickering light has been reported to be increased in migraine. In the present study, we have examined whether the VEPs are attenuated when the clinical state of the patient improves during a double-blind experiment with propranolol and femoxetine. VEPs for sinusoidally-modulated light were measured by spectral analysis, and an index depicting the visual reaction type was calculated. The group mean VEP index closely followed the group mean attack frequency, but individual variance was considerable. The changes were most evident in VEPs elicited by stimuli of about 20 Hz. During the treatments, the VEP and headache were also significantly correlated among subjects. The results suggest a close relationship between the enlarged VEPs and the headache mechanisms.     

Suppressive efficacies by adaptive temporal filtering system on photoparoxysmal response elicited by flickering pattern stimulation

PURPOSE: Based on our previous study that validated efficacies of an adaptive temporal filtering system (ATFS) suppressing a photoparoxysmal response (PPR) elicited by a chromatic flicker stimulation, we further studied ATFS efficacies on PPRs elicited by pattern-flicker stimulation in 13 photosensitive epilepsy patients. METHODS: Subjects were 13 photosensitive epilepsy patients (two male and 11 female patients; mean age +/- SD, 20.9 +/- 8.9 years) who were all sensitive to a flickering geometric-pattern scene. We used a scene consisting of 15-Hz flickering 4 c/deg stripe images lasting for 4 s. With a 14-inch television set 2 m before a subject, we displayed the following video scenes: nonfiltered and filtered flickering-stripe scenes; for the latter, two kinds of ATFSs with mild efficacy and strong efficacy were used. Three flickering-stripe scenes altogether, each of which lasted for 4 s, were given at random with a 10-s interval. RESULTS: A nonfiltered flickering-stripe scene elicited generalized PPRs in all patients; a filtered scene by use of an ATFS with mild efficacy elicited generalized PPRs in six patients (46%), whereas that by an ATFS with strong efficacy exhibited no PPRs. CONCLUSIONS: This study, using an ATFS, again shows suppressive efficacy on PPRs elicited by flickering-pattern stimulation. Therefore a series of our studies suggested that ATFS may be useful as a preventive measure for photosensitive seizures triggered by stimulative flickering images from televisions or other displays.     

Motion opponency examined throughout visual cortex with multivariate pattern analysis of fMRI data

This study explores how the human brain solves the challenge of flicker noise in motion processing. Despite providing no useful directional motion information, flicker is common in the visual environment and exhibits omnidirectional motion energy which is processed by low‐level motion detectors. Models of motion processing propose a mechanism called motion opponency that reduces flicker processing. Motion opponency involves the pooling of local motion signals to calculate an overall motion direction. A neural correlate of motion opponency has been observed in human area MT+/V5, whereby stimuli with perfectly balanced motion energy constructed from dots moving in counter‐phase elicit a weaker response than nonbalanced (in‐phase) motion stimuli. Building on this previous work, we used multivariate pattern analysis to examine whether the activation patterns elicited by motion opponent stimuli resemble that elicited by flicker noise across the human visual cortex. Robust multivariate signatures of opponency were observed in V5 and in V3A. Our results support the notion that V5 is centrally involved in motion opponency and in the reduction of flicker. Furthermore, these results demonstrate the utility of multivariate analysis methods in revealing the role of additional visual areas, such as V3A, in opponency and in motion processing more generally.     

Electroencephalographic and behavioural effects of sodium valproate in patients with photosensitive epilepsy. A single dose trial

Summary A single oral dose of Sodium valproate (VPA) given as Epilim (10 mg/kg) inhibited photoconvulsive responses, especially to 15–30 Hz frequency flicker, in seven out of ten patients with photosensitive epilepsy. In addition, in all patients (with an exception of one) the amplitude of the secondary slow negative wave of the visual evoked potentials was reduced 4–5 h after drug administration.However, in five of these patients the normalization of electrocortical reactions to a single flash and flickering light was accompanied by somnolence and fatigue, moderate slowing of EEG background, development of 3 Hz spike-wave activity and (in three patients) augmented response to hyperventilation. In two patients the EEG photoconvulsive discharge were exaggerated by VPA. These VPA effects suggest that photosensitivity and the underlying epileptic condition have overlapping albeit different pathophysiology.The data offer no support for the conclusion that reduced photosensitivity produced by VPA is associated with the therapeutic potency of the drug.     

No Evidence for Entrainment: Endogenous Gamma Oscillations and Rhythmic Flicker Responses Coexist in Visual Cortex

Over the past decades, numerous studies have linked cortical gamma oscillations (∼30–100 Hz) to neurocomputational mechanisms. Their functional relevance, however, is still passionately debated. Here, we asked whether endogenous gamma oscillations in the human brain can be entrained by a rhythmic photic drive >50 Hz. Such a noninvasive modulation of endogenous brain rhythms would allow conclusions about their causal involvement in neurocognition. To this end, we systematically investigated oscillatory responses to a rapid sinusoidal flicker in the absence and presence of endogenous gamma oscillations using magnetoencephalography (MEG) in combination with a high-frequency projector. The photic drive produced a robust response over visual cortex to stimulation frequencies of up to 80 Hz. Strong, endogenous gamma oscillations were induced using moving grating stimuli as repeatedly done in previous research. When superimposing the flicker and the gratings, there was no evidence for phase or frequency entrainment of the endogenous gamma oscillations by the photic drive. Unexpectedly, we did not observe an amplification of the flicker response around participants'' individual gamma frequencies (IGFs); rather, the magnitude of the response decreased monotonically with increasing frequency. Source reconstruction suggests that the flicker response and the gamma oscillations were produced by separate, coexistent generators in visual cortex. The presented findings challenge the notion that cortical gamma oscillations can be entrained by rhythmic visual stimulation. Instead, the mechanism generating endogenous gamma oscillations seems to be resilient to external perturbation.SIGNIFICANCE STATEMENT We aimed to investigate to what extent ongoing, high-frequency oscillations in the gamma-band (30–100 Hz) in the human brain can be entrained by a visual flicker. Gamma oscillations have long been suggested to coordinate neuronal firing and enable interregional communication. Our results demonstrate that rhythmic visual stimulation cannot hijack the dynamics of ongoing gamma oscillations; rather, the flicker response and the endogenous gamma oscillations coexist in different visual areas. Therefore, while a visual flicker evokes a strong neuronal response even at high frequencies in the gamma-band, it does not entrain endogenous gamma oscillations in visual cortex. This has important implications for interpreting studies investigating the causal and neuroprotective effects of rhythmic sensory stimulation in the gamma-band.     

Extent and time‐course of competition in visual cortex between emotionally arousing distractors and a concurrent task

Emotionally arousing cues automatically attract attentional resources, which may be at the cost of processing task‐related information. Of central importance is how the visual system resolves competition for processing resources among stimuli differing in motivational salience. Here, we assessed the extent and time‐course of competition between emotionally arousing distractors and task‐related stimuli in a frequency‐tagging paradigm. Steady‐state visual evoked potentials (ssVEPs) were evoked using random‐dot kinematograms that consisted of rapidly flickering (8.57 Hz) dots, superimposed upon emotional or neutral distractor pictures flickering at 12 Hz. The time‐varying amplitude of the ssVEP evoked by the motion detection task showed a significant reduction to the task‐relevant stream while emotionally arousing pictures were presented as distractors. Competition between emotionally arousing pictures and moving dots began 450 ms after picture onset and persisted for an additional 2600 ms. Competitive effects of the overlapping task and picture stream revealed cost effects for the motion detection task when unpleasant pictures were presented as distractors between 450 and 1650 ms after picture onset, where an increase in ssVEP amplitude to the flickering picture stimulus was at the cost of ssVEP amplitude to the flickering dot stimulus. Cost effects were generalized to all emotionally arousing contents between 1850 and 3050 ms after picture onset, where the greatest amount of competition was evident for conditions in which emotionally arousing pictures, compared to neutral, served as distractors. In sum, the processing capacity of the visual system as measured by ssVEPs is limited, resulting in prioritized processing of emotionally relevant cues.     

Neuromagnetic responses to chromatic flicker: implications for photosensitivity

Excessive cortical excitation due to visual stimulation often leads to photosensitive epilepsy. Here we demonstrate that even in normal subjects, prolonged stimulation with low-luminance chromatic (equiluminant) flicker evokes neuromagnetic activity in the primary visual cortex, which develops slowly (up to 1000 ms) and depends on the color combination of flicker. This result suggests that chromatic sensitivity is a critical factor of cortical excitation, which can be amplified over time by a flickering stimulus. We further show that transient activity occurs in the parieto-occipital sulcus as early as 100-400 ms after flicker onset, which is negatively correlated with the later occipital activity. The early parieto-occipital activity may reflect a defensive mechanism that suppresses cortical hyperactivity due to chromatic flicker.     

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.     

Development of visual function: a neurophysiological point of view

Recent findings on the development of visual function in children are summarized. First, visual evoked potentials (VEPs) in normal school children, following two types of visual stimuli (pattern reversal and light emitting diode stimulation) by transient and steady-state stimulation, are presented. Reproducible VEPs with the 4 stimulation conditions can be obtained. Transient and steady-state methods provide complementary results. Second, mechanisms for photosensitive epilepsy (PSE) are discussed. We recorded flicker VEPs to different color combinations and quantified the effects of changes in color and luminance combinations. Two amplitude peaks (9 and 18 Hz) were observed for all kinds of isoluminant color combination stimuli against temporal frequency. In addition, this characteristic was modulated by luminance. Normal children showed much higher sensitivity to contrast changes and color combination compared with normal young adults, which may be responsible for PSE in childhood. Third, cognitive function for facial expression of normal children and adults is mentioned. For Chernoff's faces showing anger and sadness produced by computer, children showed higher scores compared with adults, suggesting higher sensitivity for facial expression. Knowledge of developmental changes in children allows us to understand the maturational and degenerative changes of the central nervous system.