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Greater hemodynamic response to photic stimulation in schizophrenic patients: an echo planar MRI study.

Functional echo planar magnetic resonance imaging (MRI) probably will be of importance in assessing brain abnormalities in psychiatric disorders. The authors used functional MRI to measure the relative magnitude of the change in image signal intensity, reflecting changes in regional neuronal activity caused by photic stimulation, in eight patients with schizophrenia and nine normal comparison subjects. The mean signal intensity change in the primary visual cortex was significantly greater in patients with schizophrenia (mean = 4.6%, SD = 1.5%) than in normal comparison subjects (mean = 3.1%, SD = 1.3%). These results may reflect a variety of factors, including diffuse structural brain changes as well as primary or iatrogenic impairment of mitochondrial function or energy metabolism.

Adult↗

[Sex-related differences in EEG coherence in normal young adults--evaluation during rest and photic stimulation].

EEG coherence is a noninvasive technique for studying functional relationships between brain regions. Although EEG coherence would be a useful method to explore the differences in cerebral functional organization between the sexes, sex differences in coherence have not been well documented. The present study was conducted therefore to examine sex differences in interhemispheric EEG coherence during rest and photic stimulation (PS) in 15 male and 15 female healthy young adults. Interhemispheric coherence of the resting EEG revealed no significant sex differences for any frequency band. In contrast, coherence during PS revealed significant sex differences, and the females had a significantly higher coherence than the males in the frequency band (4.5-5.5Hz) corresponding to 5Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e., coherence reactivity) showed sex differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15Hz. These findings indicate sex differences in interhemispheric EEG coherence during PS, and provide further evidence that sex-related differences exist in the degree of lateralization of hemispheric function.

Adult↗

Structure of receptive fields of cat pulvinar neurons sensitive to photic stimulation.

Receptive fields of 262 pulvinar neurons were studied. Receptive fields of 142 of these neurons were studied in detail with the aid of a stationary spot of light, flashing in different parts of the receptive field. Depending on responses to presentation of the stationary stimulus the neurons were divided into six groups. The first group included neurons with on-off responses to photic stimulation (44 of 142), the second group neurons with off responses only (42 of 142). In cells of the third group (19 of 142) an on response only was recorded in all structures of the receptive field tested. Neurons of the fourth group (eight of 412) had a receptive field of similar structure to that of the simple receptive fields of neurons in cortical area 17. The fifth group (10 of 142) included neurons with a receptive field of concentric structure, the sixth (19 of 142) consisted of neurons with receptive fields with multiple discharge centers. The structure of the receptive field of these neurons was mosaic, with an irregular distribution of exciting and "silent" zones. The mean responses latency of the pulvinar neurons was 40-70 msec. Responses of neurons with shorter (20 msec) and longer (130-160 msec) latent periods also were recorded.

Animals↗

Mitochondrial encephalomyopathy: elevated visual cortex lactate unresponsive to photic stimulation--a localized 1H-MRS study.

We used localized H-magnetic resonance spectroscopy (MRS) to study the metabolic changes in the visual cortex of patients with mitochondrial encephalomyopathy. Measurement of metabolite levels in the occipital visual cortex obtained in the dark with seven normal subjects and with four patients (all four of whom had Kearns-Sayre syndrome [KSS]) showed high lactate levels in the patients. Photic stimulation (PS) in four normal volunteers showed that lactate increased immediately after the start of PS and that it decreased to the baseline level with continued PS. Lactate in the resting state was higher in the KSS patients than in the controls, and, unlike the controls, the KSS patients showed no significant elevation of lactate with PS.

Humans↗

Clock-gated photic stimulation of timeless expression at cold temperatures and seasonal adaptation in Drosophila.

Numerous lines of evidence indicate that the initial photoresponse of the circadian clock in Drosophila melanogaster is the light-induced degradation of TIMELESS (TIM). This posttranslational mechanism is in sharp contrast to the well-characterized pacemakers in mammals and Neurospora, where light evokes rapid changes in the transcriptional profiles of 1 or more clock genes. The authors show that light has novel effects on D. melanogaster circadian pacemakers, acutely stimulating the expression of tim at cold but not warm temperatures. This photoinduction occurs in flies defective for the classic visual phototransduction pathway or the circadian-relevant photoreceptor CRYPTOCHROME (CRY). Cold-specific stimulation of tim RNA abundance is regulated at the transcriptional level, and although numerous lines of evidence indicate that period (per) and tim expression are activated by the same mechanism, light has no measurable acute effect on per mRNA abundance. Moreover, light-induced increases in the levels of tim RNA are abolished or greatly reduced in the absence of functional CLOCK (CLK) or CYCLE (CYC) but not PER or TIM. These findings add to a growing number of examples where molecular and behavioral photoresponses in Drosophila are differentially influenced by "positive" (e.g., CLK and CYC) and "negative" (e.g., PER and TIM) core clock elements. The acute effects of light on tim expression are temporally gated, essentially restricted to the daily rising phase in tim mRNA levels. Because the start of the daily upswing in tim expression begins several hours after dawn in long photoperiods (day length), this gating mechanism likely ensures that sunrise does not prematurely stimulate tim expression during unseasonally cold spring/summer days. The results suggest that the photic stimulation of tim expression at low temperatures is part of a seasonal adaptive response that helps advance the phase of the clock on cold days, enabling flies to exhibit preferential daytime activity despite the (usually) earlier onset of dusk. Taken together with prior findings, the ability of temperature and photoperiod to adjust trajectories in the rising phases of 1 or more clock RNAs constitutes a major mechanism contributing to seasonal adaptation of clock function.

Adaptation, Physiological↗

Tyrosine phosphorylation of BIT on photic stimulation in the rat retina.

BIT is a transmembrane glycoprotein with three immunoglobulin-like domains in its extracellular region and tyrosine phosphorylation sites in its cytosolic region. We have previously shown that BIT was tyrosine phosphorylated in the hypothalamic suprachiasmatic nucleus in response to light exposure during the dark period, and suggested that it was involved in the light entrainment of the circadian clock. To further investigate the function of BIT in the nervous system, we examined the effect of photic stimulation on its tyrosine phosphorylation in the rat retina. It was found that the tyrosine phosphorylation level of BIT in the retina was higher in the light period than in the dark period. In addition, a light stimulation during the dark period resulted in a rapid phosphorylation of BIT and a subsequent association of BIT with SHP-2. The phosphorylation state was quickly reverted when the light was turned off. The light-dependent phosphorylation of BIT was also observed in isolated cultured retinas, and this was blocked by a specific Src-family inhibitor, PP-2. Immunohistochemical study showed that BIT was highly enriched in the inner and outer plexiform layers in the retina, where the immunoreactivity to anti-SHP-2 antibody was also detected. These results suggest that tyrosine phosphorylation of BIT is involved in neuronal transmission in the retina.

Animals↗

Migraine and photic stimulation: report on a survey of migraineurs using flickering light therapy.

Users of a commercial light therapy device who were using it to treat migraine were surveyed prospectively to determine what results they obtained after 30 days of daily use. Out of a total of 55 migraineurs, 44% reported that the frequency of their migraine attacks after the treatment was 'Somewhat Less' or 'Much Less' (under a conservative interpretation of these categories). Considering only the 28 migraineurs who stated that their migraine attacks were normally preceded by warning signs, 53% reported that the frequency of their migraine attacks was 'Somewhat Less' or 'Much Less'. In view of the limited efficacy and undesirable side-effects of the available migraine preventive drugs, photic stimulation (flickering light therapy) must be considered a possible preventive treatment for migraine.

Adult↗

Clinical significance of EEG abnormalities during photic stimulation in patients with photosensitive epilepsy.

PURPOSE: The continued presence of EEG abnormalities in patients with a history of photosensitive seizures is used to signify the persistence of photosensitive epilepsy. The extent to which this approach places patients at risk of seizures is unclear, however. We describe those EEG abnormalities that may be tolerated with low risk of further seizures, and those that are indicative of poor seizure control. METHODS: Fifty patients with EEG evidence of persistent photosensitive epilepsy underwent photosensitivity testing with diffuse and patterned light; 58% of patients continued to experience seizures, and 42% were seizure free. The incidence of EEG abnormalities to diffuse and patterned intermittent photic stimulation (IPS) was analysed as a function of recent seizures. RESULTS: All patients showed EEG abnormalities to patterned IPS; there was no significant association between patterned IPS and poor seizure control. EEG abnormalities to diffuse IPS occurred in 58% of patients, and 76% of these patients had experienced a seizure within the previous year. These patients were more than twice as likely to be poorly controlled than those who showed abnormalities only to patterned IPS. These results were consistent for both medicated and unmedicated patients. CONCLUSIONS: EEG abnormalities to patterned IPS can be used to signify the persistence of photosensitive epilepsy, but abnormalities to diffuse IPS are more likely to indicate the patient is poorly controlled and at risk of further seizures.

Adolescent↗

Magnitude of increase in retinal cGMP metabolic flux determined by 18O incorporation into nucleotide alpha-phosphoryls corresponds with intensity of photic stimulation.

The property of cyclic nucleotide phosphodiesterases to catalyze 3'-P--O bond cleavage and the insertion of a single nonexchangeable atom of 18O from [18O]water into the phosphoryl of the 5'-nucleotide product has been utilized as a means for measuring the hydrolytic flux of cGMP and cAMP in isolated dark-adapted intact rabbit retinas. Without illumination 18O labeling of guanine nucleotide (GTP and GDP) alpha-phosphoryls proceeds linearly for at least 80 s at a rate of 3.3 nmol of 18O/s.g of retina (wet weight). This rate is estimated to be approximately 8 times greater in the rod outer segment layer where over 90% of retinal cGMP metabolic components reside. Photic stimulation during a 20-s incubation was provided by intermittent flashes of light representing 800 ms of total illumination. Light stimuli over a range of intensities of greater than 3 log units commencing with a minimally detectable intensity produce graded increments in the rate of 18O incorporation into guanine nucleotide alpha-phosphoryls to a maximum increase of 5-fold. On the basis of only the 800-ms period of illumination this maximum increase is 125-fold. Steady state levels of retinal cGMP are not altered appreciably over this greater than 3 log range of light intensities but a light stimulus exceeding this intensity range causes an approximate 50% decrease in retinal cGMP concentration and a relative decline in the maximal rate of 18O labeling of guanine nucleotide alpha-phosphoryls. No light-related increases were detected in 18O incorporation into adenine nucleotide alpha-phosphoryls nor the gamma-phosphoryls of GTP or ATP or Pi. These observations indicate that light stimuli over greater than 3 log of light intensity produce incremental increases in cGMP metabolic flux that result from comparable increases in the rates of both cGMP generation and cGMP hydrolysis. It is postulated that increases in cGMP metabolic flux rather than changes in cGMP steady state levels are integral to phototransduction by a mechanism that involves the coupling of cGMP synthesis and/or hydrolysis to either the release of calcium from disc membranes or the inhibition of Na+ conductance by the photoreceptor membrane. This is suggested to occur by an energy-linked process and/or the generation of protons.

Adenine Nucleotides↗

Timing of puberty and EEG coherence during photic stimulation.

Selective elimination of a large proportion of cortical synapses constitutes the last major stage in brain development which is linked to sexual maturation. Various neurodevelopmental theories have proposed an association between schizophrenia and late brain maturational events. Based on epidemiological and psychopharmacological data, Saugstad hypothesised a relationship between timing of puberty, synaptic density and psychosis proneness. Early puberty should result in an earlier end to synaptic pruning, a larger number of surviving connections and an increased risk for affective psychosis. In contrast, in late maturers prolonged synapse elimination should lead to lower synaptic density which constitutes a diathesis for schizophrenia. We used EEG coherence as a neurophysiological measure of cortico-cortical connectivity. Late maturers were expected to show higher coherence, especially for short-distance connections where lower synaptic density should lead to decreased local differentiation. EEG was recorded from 12 bipolar derivations in 19 early and 19 late maturing subjects of both sexes under conditions of rest and photic stimulation at different flicker frequencies. Whereas there were no coherence differences between early and late maturers during rest, both groups differed during flicker stimulation. As hypothesised, late maturers were found to have higher short-distance coherence. Late maturers were also found to have higher intrahemispheric long-distance coherence. These findings were restricted to delta, alpha and beta 2 bands and were more pronounced in males. Our findings are interpreted in terms of a structural difference in neuronal connectivity between extreme early and late maturers.

Adult↗

Age-dependent change in metabolic response to photic stimulation of the primary visual cortex in infants: functional magnetic resonance imaging study.

The blood oxygen level-dependent (BOLD) response to photic stimulation in the primary visual cortex (V1) reverses from positive to negative around 8 weeks of age. This phenomenon may be caused by increased oxygen consumption during stimulation as the result of a rapid increase of synaptic density at this age. To test this hypothesis, we applied existing mathematic models of BOLD signals to the experimental data from infants. When the stimulus-related increments of cerebral blood flow and cerebral blood volume were fixed at 60% and 20%, respectively, the mean estimated increment of the cerebral metabolic rate of oxygen of the V1 in the elder infant group (57.1% +/- 8.8%) was twice as large as that in the younger infant group (32.2% +/- 4.7%), which corresponds to the reported difference in synaptic density. The present data confirmed that a change in oxygen consumption could explain a transition from a positive to a negative BOLD response.

Age Factors↗

EEG harmonic responses to photic stimulation in normal aging and Alzheimer's disease: differences in interhemispheric coherence.

OBJECTIVES: The distinction between electroencephalogram (EEG) driving responses in normal aging and Alzheimer's disease (AD) is unclear. This study was conducted to explore the structure of harmonic responses of EEG coherence during photic stimulation (PS) in AD. METHODS: EEG interhemispheric coherence was analyzed for each harmonic responses during PS (white flickers at 5, 10 and 15 flashes/sec) in younger subjects (20-25 years), non-demented elderly subjects (50-67 years) and AD patients (43-66 years). RESULTS: The elderly subjects had higher interhemispheric coherence during PS than the younger subjects, with significant differences found in the 6th (30Hz) and 8th (40Hz) harmonic responses to 5Hz PS. The AD patients had significantly smaller coherence than the elderly subjects in the 2nd (10Hz) and 4th (20Hz) harmonic responses to 5Hz PS, and in the fundamental (10Hz) and 2nd (20Hz) harmonic responses to 10Hz PS. These coherence values did not correlate with duration of the disease or with cognitive functioning as evaluated by MMSE score. CONCLUSIONS: A failure of stimulation-related brain activation in AD patients was observed in alpha-related frequencies, suggesting that AD is not the end result of normal aging of the brain, at least in terms of the mechanisms which are involved in PS-related functional organization.

Aged↗

Synthesis and degradation of retinal proteins in darkness and during photic stimulation.

Rabbit retinas were maintained in a physiological state in vitro and exposed to 0.5-h pulses of labeled leucine. Protein synthesis was determined from incorporation of the label, and degradation from its subsequent release. The retinas were treated as test-control pairs. The control retina remained in darkness while the test retina was subjected to photic stimulation, either during labeling to determine the effect on synthesis or after labeling to determine the effect on degradation. 3H and 14C alternated as test and control labels. The two retinas were combined for solubilization. Their proteins were separated according to size by gel electrophoresis. Each gel was cut into 95 slices and each slice was differentially counted. The isolated retinas synthesized new protein rapidly and reproducibly. The average S.D. of the isotope ratios measured on gel slices from replicate experiments was 2.2% of the mean. Retinas driven by flashing light of constant intensity exhibited a marked increase in ganglion cell firing and accumulated 38% more (p = 0.005) 2-deoxyglucose than their controls kept in darkness. However, they did not differ from the controls in the incorporation of labeled leucine into total protein or into any of the protein fractions separated on the gel, the largest deviation from unity in the 95 test-control ratios being 1.7%. Continuous light and flashing light of increasing intensity also markedly affected function and energy metabolism, but had no significant effects on leucine incorporation. None of the stimuli affected degradation, though the experiments would have been less sensitive to a change in degradation that to a change in synthesis. These results indicate that the synthesis and degradation of proteins are little affected by a marked increase in functional activity.

Animals↗