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Photic stimulation inhibits growth hormone secretion in rats: a hypothalamic mechanism for transient entrainment.

It is well established that photic cues are used by the suprachiasmatic nucleus (SCN) to entrain circadian rhythms to the light/dark cycle, but the role of photic stimuli in the regulation of ultradian neuroendocrine rhythms is ill defined. In relation to the rhythms of GH secretion, recent studies have shown that nocturnal photic stimulation induces gene expression not only in the SCN but also in periventricular (PeN) somatostatin (SRIF) neurons. We have, therefore, investigated the effect of nocturnal photic stimulation on spontaneous and induced GH secretion in conscious rats. Nocturnal photic stimulation (lights on at 2400 h for 1 h) suppressed spontaneous GH secretion in male and female rats and reduced the GH response to SRIF withdrawal and iv injection of GH-releasing factor. A similar trough in GH secretion was also observed during the first hour of the normal light phase (0600 h). Using immunohistochemical analysis, we have also shown that expression of the transcription factor, Egr-1, is induced at the commencement of the light phase in the SCN, PeN, and medial preoptic nucleus. This effect is abolished by maintaining rats in the dark during this period. These data, together with our previous demonstration that 50% of SRIF-positive neurons in the PeN coexpress Egr-1 after photic stimulation, suggest that activation of SRIF neurons in the PeN may entrain the episodes of GH secretion to the dark/light interface. However, the absence of synchrony in GH pulses between animals by the second half of the light period suggests that this entrainment is transient.

Animals↗

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Electroencephalography↗

[Assessment of brain cell function using 123I-IMP SPECT of cerebral blood flow and visual evoked potential by photic stimulation in normal and demented elderly subjects].

Cerebral blood flow was quantitatively measured using 123I-IMP SPECT by photic stimulation and visual evoked potential (VEPs) in normal and dementia subjects: 8 with Alzheimer-type dementia, 9 with cerebrovascular dementia and 7 normal elderly subjects were divided into the three groups based on the Clinical Dementia Rating (CDR) grade: Group I (CDR 0), Group II (CDR 0.5-1), Group III (CDR 2-3). The 123I-IMP SPECT measurement was conducted at rest with the eyes closed and also during photic stimulation. VEPs were measured simultaneously. The results reveal prolongation of the P2 latency of the VEPs prolonged in accordance with the increasing severity of the dementia, and quantitative cerebral blood flow was lower in Group II and Group III than in Group I at rest, while during photic stimulation it significantly increased in Group I and II, but showed no change in Group III. The results suggest that quantitative measurement of cerebral blood flow using 123I-IMP SPECT by photic stimulation may enable more detailed assessment of brain cell function.

Aged↗

[Motor responses of rabbits to repeated photic stimulation].

In response to a repeated photic stimulation of moderate intensity EMG-responses appeared in neck, ear, fore- and hind-limbs muscles of a rabbit, with no tendency to extinction. Animal's position had a considerable effect on the probability of occurence of EMG-responses. The probability was similar for all muscles, making 30% when the rabbit was fixed in a lying position (posture I) and about 15% when the animal was in a natural sitting position (posture II). The response latencies, recorded in limb muscles, varied considerably, the distribution maximum occurring at 0.4--0.6 sec. In rabbits in posture I the fore-leg was involved into reaction more rapidly than the hind-leg. In rabbits in posture II no such difference was observed. It is assumed that EMG-responses to indifferent stimuli reflect rearrangements occuring primarily in the postural system and contributing to animal's activity readiness.

Acoustic Stimulation↗

Convergence of finger tremor and EEG rhythm at the alpha frequency induced by rhythmical photic stimulation.

The frequencies of EEG alpha rhythm and physiological finger tremor overlap at 9-10 c/sec, suggesting a functional relationship between the two mechanisms. We measured the correlation between the two rhythms when they occurred spontaneously and when rhythmical photic stimulation was applied. Rhythmical physiological finger tremor (9.7 c/sec +/- 1.06 S.D.) was accompanied by an alpha rhythm (10.3 c/sec +/- 0.51 S.D.) spontaneously, showing a one-to-one relationship at times. When photic stimulation was provided at a frequency (11 Hz) close to the subject's spontaneous alpha rhythm, a frequency-convergence occurred between finger tremor (10.3 c/sec +/- 0.68 S.D.) and the EEG (10.6 c/sec +/- 0.35 S.D.). The correlation coefficient between the two rhythms under photic stimulation was significantly higher (0.49 +/- 0.14 S.D.) than under the spontaneous condition (0.13 +/- 0.16; P less than 0.05). Consistent with this, the mean difference between finger tremor and EEG frequencies was significantly lower during photic stimulation (0.83 c/sec +/- 0.46 S.D.) than during the spontaneous condition (1.23 c/sec +/- 0.82 S.D.) (t = 2.54; P less than 0.05, t-test for correlated means). These findings indicate that the EEG and physiological finger tremor tend toward synchrony with each other in an environment of photic stimulation, supporting our hypothesis of a functional relationship between the two mechanisms.

Adult↗

N-methyl-D-aspartate, quisqualate and kainate receptors are all involved in transmission of photic stimulation in the suprachiasmatic nucleus in rats.

In order to clarify the neuronal transmission mechanism of photic stimulation in the suprachiasmatic nucleus (SCN), the effects of agonists and antagonists for excitatory amino acid receptors on N-acetyltransferase (NAT) activity in the pineal gland were observed following the microinjection of drugs into both sides of the nuclei. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate (which are selective agonists for three different subtypes, i.e. NMDA, quisqualate and kainate receptors, respectively) significantly decreased NAT activity similarly to the suppressive effect of light. Moreover, compared with a control group, all the groups pretreated with a selective competitive antagonist for NMDA receptor (D-2-amino-5-phosphonovalerate or 3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonate), or a selective non-competitive antagonist for non-NMDA receptors (Joro spider toxin-3 or 1-naphthylacetyl spermine) partially blocked the suppressive effect of photic stimulation on NAT activity. These results suggest that NMDA, quisqualate and kainate receptors are all involved in mediating photic stimulation in the SCN.

Acetyltransferases↗

Adenosine enhances functional activation of blood flow in cat optic nerve head during photic stimulation independently from nitric oxide.

Blood flow studies in the brain, heart, and other organs suggest that there could be interaction between nitric oxide (NO) and adenosine. This possibility was investigated in the optic nerve head (ONH) during photic stimulation of the dark-adapted cat eye. Functional activation of ONH blood flow was measured by laser Doppler flowmetry, simultaneously with NO and PO(2) using double-barrel recessed electrochemical sensors. Photic stimulation (diffuse luminance flickering light at 30 Hz) increased ONH blood flow to 127.4 +/- 4.7% (mean +/- SEM) of baseline with a transient increase in NO by 79.8 +/- 12.8 nM, while PO(2) decreased from 24.5 +/- 2.7 to 22.7 +/- 2.4 Torr (control responses, 15 trials, 10 cats). Adenosine (3 mg/kg iv) increased baseline ONH blood flow to 113.8 +/- 8.4% of control within 5 min. Functional activation of ONH blood flow was enhanced during photic stimulation, reaching a maximum of 155.8 +/- 8.1% within 5 min, and remained enhanced for 30 to 45 min. NO responses during photic stimulation were not different from control responses. Treatment with a nonspecific NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester, 40 mg/kg iv, 5 cats) did not alter the increase in resting ONH blood flow or the enhanced functional activation after adenosine. We conclude that there is no interaction between NO and adenosine during functional activation of cat ONH blood flow by photic stimulation.

Adenosine↗

Effects of frequency of photic stimulation upon autistic and retarded children.

The present study was designed to determine if frequency of repetitive photic stimulation could affect the response rate of an operant upon which such stimulation was made contingent. To test this hypothesis, we trained retarded and autistic children, equated for mental age, to pull a lever to obtain photic stimulation of different frequencies. It was found that (a) response rates of autistic children were related to the frequency of stimulation, while retarded children showed no such consistency. (b) The two groups did not differ in the average duration of time they engaged in stereotypies. (c) During a subsequent extinction session, two autistic children ceased responding, but one of two retarded children did not. (d) Noncontingent photic stimulation suppressed a food-motivated operant in one autistic child. These results were interpreted as evidence for frequency-dependent properties of repetitive visual feedback in autistic children. In addition, support was given to the position that performance deficits in autistic children correlating with the occurrence of stereotypies result from competition of different sources of reinforcement.

Age Factors↗

Reduced interhemispheric EEG coherence in Alzheimer disease: analysis during rest and photic stimulation.

The present study was conducted to examine interhemispheric electroencephalogram (EEG) coherence at rest and during photic stimulation (5, 10, and 15 Hz) in 10 patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 56 years) and 10 sex- and age-matched control subjects. Compared with the control subjects, the AD patients had significantly lower interhemispheric coherence in the resting EEG for the delta, theta-2, alpha, and beta-1 frequency bands. EEG analysis during photic stimulation also showed that the patients had significantly lower coherence, irrespective of the stimulus frequency. In addition, when we examined the changes in coherence from the resting state to the stimulus condition (i.e., coherence reactivity), significant group differences were found at the brain region primarily involved in visual functioning; the patients had significantly smaller coherence reactivity to photic stimulation at 5 and 15 Hz over the posterior regions. These findings suggest that AD patients have an impairment of interhemispheric functional connectivity in both nonstimulus and stimulus conditions. The findings also suggest a failure of normal stimulation-related brain activation in AD.

Aged↗

Auditory potentials elicited by the grass photic stimulator in the rat.

Flash visual evoked potentials were recorded from the rat to determine whether the Grass photic stimulator could generate an auditory component of the waveform. When the click associated with each lamp flash remained unmuffled, the primary response of the visual cortex (P30) was preceded by an earlier positivity with a latency between 6-8 ms. When the photic stimulator lamp was subsequently insulated in order to deaden the sound of the click, the P30 potential remained intact while the earlier response disappeared. It is concluded that the photic stimulator is capable of eliciting a distinct auditory potential of probable collicular origin.

Animals↗

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.

Adult↗

Haloperidol abolished glutamate release evoked by photic stimulation of the visual cortex in rats.

There is evidence that systemic administration of haloperidol, a dopamine receptor blocker, attenuates visual cortex evoked potentials. However, there is scarce information on cortical neurochemical changes associated with haloperidol effects on visual function. The present experiment was designed to investigate: (1) the effect of photic stimulation on glutamate release in the visual cortex; and (2) whether systemic administration of haloperidol would affect those neurochemical changes. Microdialysis probes were implanted in the occipital cortex. Glutamate levels were measured every 30 s using capillary zone electrophoresis. Extracellular glutamate levels increased to about 282% 30 s after photic stimulation started and remain elevated for the 3 min that the photic stimulation lasted. Haloperidol (1.5 and 5 mg/kg, i.p.) completely suppressed the increased of glutamate efflux during photic stimulation. Finally, it was also found that the highest dose of haloperidol (5 mg/kg) did not change glutamate basal levels. The results are discussed with reference to possible dopaminergic actions on the visual system function.

Animals↗

Altered brain energy metabolism in lithium-resistant bipolar disorder detected by photic stimulated 31P-MR spectroscopy.

BACKGROUND: Previous 31P-MRS (magnetic resonance spectroscopy) studies suggested altered brain energy metabolism in bipolar disorder. This study characterized brain energy metabolism in lithium-resistant bipolar disorder using the photic-stimulation paradigm. METHODS: Subjects were 19 patients with DSM-IV bipolar disorder (nine responders and 10 nonresponders, 13 with bipolar I and six with bipolar II) in the euthymic state and 25 healthy volunteers. Energy metabolism in the occipital region was examined by 31P-MRS during photic stimulation (PS). Six 31P-MR spectra were obtained, one was before PS (Pre), two during 12 min of PS (PS1, PS2), and three after the PS (Post 1, Post 2, Post 3). RESULTS: Significant effect of diagnosis (lithium-responsive bipolar disorder, lithium-resistant bipolar disorder, and control) was found for the phosphocreatine peak area ratio during the course of the photic stimulation (P < 0.05 by repeated measures ANOVA). The phosphocreatine peak area ratio was significantly decreased at Post 1 and Post 2 compared with Pre in lithium-resistant bipolar patients (P = 0.01 and P = 0.01 by Dunnett's multiple comparison). CONCLUSIONS: The finding that phosphocreatine decreased after photic stimulation may be compatible with mitochondrial dysfunction. It is possible that mitochondrial function is impaired in lithium-resistant bipolar disorder.

Adult↗

Slow-wave photic stimulation relieves patient discomfort during esophagogastroduodenoscopy.

BACKGROUND AND AIM: Although pretreatment with a sedative drug is effective in relieving pain during esophagogastroduodenoscopy (EGD), such drugs can cause significant side-effects. The aim of this study was to examine the effect of slow-wave photic stimulation on discomfort and/or pain felt during EGD. METHODS: Forty consecutive patients (25 men and 15 women) who underwent diagnostic EGD in our hospital were included in the study. Twenty patients received photic stimulation for 25 min, and underwent electroencephalographic recording, in addition to the usual premedications. Twenty control patients received the same treatment but without photic stimulation. All patients evaluated the discomfort/pain felt during endoscopy against a five-grade scale in comparison with what they had experienced in their previous examination. RESULTS: Patients with an improved discomfort/pain score were 18/20 and 3/20 in the treated and control groups, respectively. Overall comparison of pain scores between both groups was significant (P<0.0001). The proportion of slow-wave activity recorded in patients' electroencephalograms significantly increased in the treated group compared to control values (36.6+/-6.8% vs 29.1+/-3.4%, P<0.001). There was a close correlation between the degree of discomfort/pain felt during endoscopy and the proportion of slow-wave activity (P<0.001). CONCLUSION: Slow-wave photic stimulation shows promise as a treatment for relieving the discomfort and/or pain felt by patients undergoing EGD.

Adult↗

Posterior hypothalamic deafferentation or 5,7-dihydroxytryptamine inhibit corticotropin-releasing hormone, ACTH and corticosterone responses following photic stimulation.

The effect of posterior hypothalamic deafferentation (PHD) or hypothalamic serotonin (5-HT) depletion by 5,7-dihydroxytryptamine on corticotropin-releasing hormone (CRH), ACTH and corticosterone (CS) responses, following photic stimulation, was investigated in male rats. In intact animals, photic stimulation caused median eminence (ME) CRH depletion and a rise in serum ACTH and CS levels. In rats with PHD, in which previous studies have demonstrated 5-HT depletion, or with neurotoxin induced hypothalamic 5-HT reduction, these responses were markedly inhibited. This indicates that the blockage in the release of ME CRH into the portal circulation in rats with hypothalamic 5-HT depletion is responsible for the inhibition of the pituitary-adrenocortical responses following photic stimulation.

5,7-Dihydroxytryptamine↗

NGFI-A gene expression induced in the rat suprachiasmatic nucleus by photic stimulation: spread into hypothalamic periventricular somatostatin neurons and GABA receptor involvement.

We studied NGFI-A gene expression in response to photic stimulation in the rat suprachiasmatic nucleus (SCN) using in situ hybridization histochemistry. This gene expression spread within the SCN and extended dorsally into the anterior hypothalamus after 30 min-1 h of light exposure at circadian time (CT) CT18. It appeared first in the ventrolateral SCN where the retinohypothalamic tract (RHT) innervates, then it expanded dorsomedially in the SCN and beyond the SCN to the anterior hypothalamus. However, stimulation for 2 h light exposure decreased its expression in the SCN. NGFI-A expression in the somatostatin neurons in the periventricular nucleus increased from 8.7% to 41% with increasing exposure time from 5 to 30 min. NGFI-A mRNA expression in the SCN was suppressed by pretreatment with baclofen, the GABAB receptor agonist. The spread of photic information from the retina to the SCN was visualized at immediate early gene level not only in the SCN but also in the area beyond the SCN. Somatostatin neurons in the periventricular nucleus which project to the external layer of the median eminence and are involved in regulation of growth hormone release showed NGFI-A gene expression corresponding to the duration of photic stimulation. Photic-induced NGFI-A gene expression in the SCN was also shown to be regulated by GABAergic transmission via GABAB receptors. These NGFI-A gene-expressing cells in the SCN may be involved in the circadian entrainment by light and some of those outside the SCN may participate in the regulation of neuroendocrine function.

Animals↗

Spectral analysis of photic stimulation in migraine.

In seeking an electrophysiologic discriminator of migraine, we applied computer technology to power spectral analysis of the EEG with photic stimulation. In 11 normal volunteers and 11 migraineurs (both classic and common) we were able to classify all migraineurs and misclassified only one normal based on the spectral analysis. The discriminator contained 5 elements: the increased driving power of migraineurs with photic stimulation at 24 flashes/sec, 34 flashes/sec, and 38 flashes/sec; and the increased power in the alpha band in both parietal and occipital leads at 20 flashes/sec. Power spectral analysis in conjunction with photic stimulation may provide the necessary data for effective discrimination of migraine from non-migraine states.

Adult↗

Preliminary trial of photic stimulation for premenstrual syndrome.

In an open study 17 women with confirmed, severe and long-standing premenstrual syndrome used photic stimulation with a flickering red light, every day for up to four menstrual cycles. At the end of treatment prospectively recorded median luteal symptom scores were reduced by 76% (95% confidence interval 54-93, P < 0.001), with clinically and statistically significant reductions for depression, anxiety, affective lability, irritability, poor concentration, fatigue, food cravings, bloating and breast pain. Twelve of the 17 patients (71%) no longer had the premenstrual syndrome. One patient failed to improve. One patient withdrew because of worsening premenstrual depression, but photic stimulation was otherwise well tolerated. The improvement is greater than that reported for relaxation or in open studies of fluoxetine, and much more than historical placebo rates. Photic stimulation may be a useful treatment for the premenstrual syndrome, and by its suggested action on circadian rhythms may have wider therapeutic applications.

Journal Article↗