Dosimetry in cranial photobiomodulation therapy: effect of cranial thickness and bone density.

This research aims to examine the influence of human skull bone thickness and density on light penetration in PBM therapy across different wavelengths, focusing on how these bone characteristics affect the absorption of therapeutic light. Analyses explored the effect of skull bone density and thickness on light penetration in PBM, specifically using Low-Level Laser Therapy (LLLT) for efficacy prediction. Measurements of bone thickness and density were taken using precise tools. This approach emphasizes LLLT's significance in enhancing PBM outcomes by assessing how bone characteristics influence light penetration. The study revealed no significant correlation between skull bone density and thickness and light penetration capability in photobiomodulation (PBM) therapy, challenging initial expectations. Wavelengths of 405 nm and 665 nm showed stronger correlations with bone density, suggesting a significant yet weak impact. Conversely, wavelengths of 532 nm, 785 nm, 810 nm, 830 nm, 980 nm, and 1064 nm showed low correlations, indicating minimal impact from bone density variations. However, data variability (R2 < 0.4) suggests that neither density nor thickness robustly predicts light power traversing the bone, indicating penetration capability might be more influenced by bone thickness at certain wavelengths. The study finds that the effectiveness of photobiomodulation (PBM) therapy with bone isn't just based on bone density and thickness but involves a complex interplay of factors. These include the bone's chemical and mineral composition, light's wavelength and energy dose, treatment duration and frequency, and the precise location where light is applied on the skull.

Photobiomodulation increases brain metabolic activity through a combination of 810 and 660 wavelengths: a comparative study in male and female rats.

Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to benefit the nervous system by modifying the mitochondrial cytochrome c-oxidase (CCO) enzyme, which has red (620-680 nm) or infrared (760-825 nm) spectral absorption peaks. The effect of a single 810-nm wavelength with a combination of 810 nm and 660 nm lights in the brain metabolic activity of male and female rats was compared. PBM, with a wavelength of 810 nm and a combination of 810 nm and 660 nm, was applied for 5 days on the prefrontal cortex. Then, brain metabolic activity in the prefrontal area, hippocampus, retrosplenial, and parietal cortex was explored. Sex differences were found in cortical and subcortical regions, indicating higher male brain oxidative metabolism, regardless of treatment. CCO activity in the cingulate and prelimbic area, dentate gyrus, retrosplenial and parietal cortex was enhanced in both treatments (810 + 660 nm and 810 nm). Moreover, using the combination of waves, CCO increased in the infralimbic area, and in CA1 and CA3 of the hippocampus. Thus, employment of a single NIR treatment or a combination of red to NIR treatment led to slight differences in CCO activity across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.

No Effects of Photobiomodulation on Prefrontal Cortex and Hippocampal Cytochrome C Oxidase Activity and Expression of c-Fos Protein of Young Male and Female Rats.

The role of light in our biological processes and systems is extensively known. In addition, the use of light devices has been introduced in the field of healthcare as an opportunity to administer power light at specific wavelengths to improve our body functions and counteract light deficiency. One of these techniques is photobiomodulation (PBM), which uses red to infrared light in a non-invasive way to stimulate, heal, regenerate, and protect tissue. The main proposed mechanism of action is the stimulation of the cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial electron transport chain. PBM has achieved positive effects on brain activity and behavioral function of several adult animal models of health and disease, the potential use of this technique in developing stages is not surprising. This research aims to examine the effects of PBM on the prefrontal cortex and hippocampus of 23 day-old healthy male (n = 31) and female (n = 30) Wistar rats. Three groups of each sex were used: a PBM group which received 5 days of PBM, a device group submitted to the same conditions but without light radiation, and a control basal group. CCO histochemistry and c-Fos immunostaining were used to analyze brain metabolic activity and immediate early genes activation, respectively. Results displayed no metabolic differences between the three groups in both sexes. The same results were found in the analysis of c-Fos positive cells, reporting no differences between groups. This research, in contrast to the PBM consequences reported in healthy adult subjects, showed a lack of PBM effects in the brain markers we examined in young healthy rat brains. At this stage, brain function, specifically brain mitochondrial function, is not disturbed so it could be that the action of PBM in the mitochondria may not be detectable using the analysis of CCO activity and c-Fos protein expression. Further studies are needed to examine in depth the effects of PBM in brain development, cognitive functions and postnatal disorders, along with the exploration of the optimal light parameters.

Methylene blue and photobiomodulation recover cognitive impairment in hepatic encephalopathy through different effects on cytochrome c-oxidase.

Mitochondrial dysfunction plays a central role in hepatic encephalopathy (HE), due to changes in enzyme cytochrome c-oxidase (CCO), causing a decline in brain metabolism. We used an HE animal model and applied intracranial administration of methylene blue (MB) and transcranial photobiomodulation (PBM), both targeting CCO, to determine their differential effects on recovering cognition. Five groups of rats were used: sham-operated group + saline (SHAM + SAL, n = 6), hepatic encephalopathy + SAL (HE + SAL, n = 7), SHAM + methylene blue (SHAM + MB, n = 7), HE + MB (n = 7), HE + PBM (n = 7). PBM animals were exposed transcranially to 670 +/- 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days, and the MB and SAL groups were injected with 2.2 µg/0.5 µL in the accumbens. Cognitive dysfunction was evaluated on a striatal stimulus-response task using the Morris water maze. Our results showed cognitive improvement in the HE group when treated with MB. This improvement was accompanied by a decrease in CCO activity in the prefrontal cortex, dorsal striatum, and dorsal hippocampus. When comparing MB and PBM, we found that, although both treatments effectively improved the HE-memory deficit, there was a differential effect on CCO. A general decrease in CCO activity was found in the prefrontal and entorhinal cortices, dorsal striatum, and hippocampus when PBM, compared to MB, was applied. Our results suggest that mitochondrial dysfunction and brain metabolic decline in HE might involve CCO alteration and can be improved by administering MB and PBM.

Photobiomodulation as a promising new tool in the management of psychological disorders: A systematic review.

Photobiomodulation is a brain modulation technique that has become a promising treatment for multiple pathologies. This systematic review collects studies up to 2019 about the beneficial effects of photobiomodulation as a therapy for treating psychological disorders and a tool for modulating cognitive processes. This technique is mostly used for the treatment of depression and stress, as well as to study its effects on psychological variables in healthy subjects. Despite the lack of parameters used, photobiomodulation seems to achieve enough brain penetration to produce beneficial effects in healthy subjects and patients with multiple pathologies. The best parameters are the wavelengths of 810 nm for the treatment of depression and 1064 nm for cognitive enhancement, along with a scalp irradiance of 250 mW/cm2 and a scalp yield of 60 J/cm2. It weekly application on the bilateral prefrontal area and the default mode network seems to be ideal for the maintenance of the effects. Photobiomodulation could be used as an effective and safe therapy for the treatment of multiple psychological pathologies.

Photobiomodulation rescues cognitive flexibility in early stressed subjects.

Neglectful parenting is one of the most prevalent forms of child mistreatment. This early life stress leads to long-term alterations in all the psychological domains, as well as brain alterations. Animal models have been developed to emulate and further study this early life stress, and one of most widely used models is maternal separation. In both human and animal models, cognitive flexibility has been found to be altered. In this study, we performed maternal separation (10 days, 4 h per day) in rats, and in adulthood, we tested their spatial navigation and cognitive flexibility. In addition, we delivered photobiomodulation treatment (Low-level light therapy: 1064 nm, 30 mW, 60 cycles) on the rats' brains, and we tested energy oxidative metabolism using cytochrome c oxidase histochemistry. Early life stress delivered in the form of maternal separation on the first 10 postnatal days leads to cognitive flexibility impairment and a general increase in energy metabolism in adulthood. Low-level light therapy seems to be useful for treating these unwanted outcomes, because it rescued cognitive flexibility and returned the oxidative energy metabolism to balanced scores, without harming controls' brains or behavior. Photobiomodulation is a promising tool in the treatment of chronic stress-related consequences because it rescued cognitive flexibility.

The Psychoexposome: A holistic perspective beyond health and disease / Psicoexposoma: una perspectiva holística más allá de la salud y la enfermedad

Background: The concept of the exposome has emerged as a new strategy for studying all environmental exposures throughout an individual’s life and their impact on human health. Nowadays, electronic devices are available to collect data about an individual’s geolocation, biological function, or exposure biomarkers. The appearance of "omic" sciences and advances in bioinformatics have allowed massive data-gathering and analysis from various scientific fields. Objective: to propose the term Psychoexposome in line with the concept of the exposome from the field of environmental sciences. Method: a literature review of psychological terms associated with the exposome concept was carried out and the rationale and benefits of a psychoexposme approach for psychological sciences is discussed. Results: the terms psychology, psychiatry and neurological diseases are scarce in the exposome approach. A long tradition in psychology of performing epidemiological studies and in the study of multifactorial influences traits places psychologists at an advantageous starting point for conducting psychoexposome studies. Conclusion: psychology may take advantage from both exposome and omic sciences to create an integrated psychoexposome approach that may help in deciphering the etiology of psychological disorders and improving people's mental health (AU)

Antecedentes: el concepto de exposoma surgió como una estrategia para impulsar el estudio exhaustivo de las exposiciones ambientales a lo largo de la vida del individuo y su impacto en la salud. El desarrollo de dispositivos electrónicos para obtener datos de geolocalización, biológicos o biomarcadores de exposición y los avances en las ciencias "ómicas" y en bioinformática permiten la recopilación y el análisis masivo de datos muy diversos. Objetivo: proponer el término psicoexposoma en línea con el concepto de exposoma generado desde las ciencias ambientales. Método: se llevó a cabo una revisión de la literatura para buscar la inclusión de términos psicológicos asociados al concepto de exposoma. Se discute la justificación de un enfoque de psicoexposición para las ciencias psicológicas. Resultados: los términos psicología, psiquiatría o enfermedades neurológicas son escasos en el enfoque del exposoma. La experiencia en el control de variables ambientales sitúa al psicólogo en un punto de partida ventajoso para realizar estudios de psicoexposoma. Conclusión: la psicología puede aprovechar tanto las ciencias de la exposición como las ciencias "ómicas" para crear un enfoque integrado de psicoexposición que pueda ayudar a descifrar la etiología de los trastornos psicológicos y a promover la salud mental del individuo (AU)

The Psychoexposome: A holistic perspective beyond health and disease.

BACKGROUND: The concept of the exposome has emerged as a new strategy for studying all environmental exposures throughout an individual’s life and their impact on human health. Nowadays, electronic devices are available to collect data about an individual’s geolocation, biological function, or exposure biomarkers. The appearance of “omic” sciences and advances in bioinformatics have allowed massive data-gathering and analysis from various scientific fields. OBJECTIVE: to propose the term Psychoexposome in line with the concept of the exposome from the field of environmental sciences. METHOD: a literature review of psychological terms associated with the exposome concept was carried out and the rationale and benefits of a psychoexposme approach for psychological sciences is discussed. RESULTS: the terms psychology, psychiatry and neurological diseases are scarce in the exposome approach. A long tradition in psychology of performing epidemiological studies and in the study of multifactorial influences traits places psychologists at an advantageous starting point for conducting psychoexposome studies. CONCLUSION: psychology may take advantage from both exposome and omic sciences to create an integrated psychoexposome approach that may help in deciphering the etiology of psychological disorders and improving people’s mental health.

Low-light-level therapy as a treatment for minimal hepatic encephalopathy: behavioural and brain assessment.

Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments involved in MHE. We studied one of its precipitating factors, portal hypertension. The purpose was to evaluate an enhancement in neuronal metabolism through low-light-level therapy (LLLT) and whether this therapy has effects on behavioural task acquisition. Rats were trained to perform a stimulus-response task using the Morris water maze. Three groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal vein ligation method was used to create an animal model of the early developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days. The metabolic activity of the brains was studied with cytochrome c oxidase histochemistry. There were differences in behavioural performance, with an improvement in the PH + LLLT group. Energetic brain metabolism revealed significant differences between the groups in all the brain structures analysed, except the anterodorsal thalamus. At the same time, in different brain networks, the PH group showed a more complicated relationship among the structures, while the SHAM and PH + LLLT groups had similar patterns. In this study, we provide the first preliminary insights into the validity of LLLT as a possible intervention to improve memory under minimal hepatic encephalopathy conditions.

The importance of the context in the hippocampus and brain related areas throughout the performance of a fear conditioning task.

The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and retention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and retention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and retention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer retention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology, including post-traumatic stress disorder, schizophrenia, and substance abuse disorders.

Sexual metabolic differences in the rat limbic brain.

BACKGROUND: There is actually limited evidence about the influence of estrogens on neuronal energy metabolism or functional cerebral asymmetry. In order to evaluate this relationship, eight male and sixteen female adult Wistar rats, divided into estrus and diestrus phase, were used to measure basal neuronal metabolic activity in some of the structures involved in the Papez circuit, using cytochrome c oxidase (C.O.) histochemistry. METHOD: We used C.O. histochemistry because cytochrome oxidase activity can be considered as a reliable endogenous marker of neuronal activity. RESULTS: We found higher C.O. activity levels in diestrus as compared to estrus and male groups in the prefrontal cortex and thalamus. Conversely, neuronal oxidative metabolism was significantly higher in estrus than in diestrus and male groups in the dorsal and ventral hippocampus (CA1 and CA3) and in the mammillary bodies. However, no hemispheric functional lateralization was found in estrus, diestrus or male groups by C.O. activity. CONCLUSIONS: These results suggest a modulatory effect of estrogens on neuronal oxidative metabolism.

Memory performance and scopolamine: hypoactivity of the thalamus revealed by cytochrome oxidase histochemistry.

Spatial memory learning is related to the functioning of a neuronal circuit composed of cortical, hippocampal and diencephalic brain regions. The Morris water maze (MWM) is frequently used to assess spatial memory in rats. In this study, the neuronal functional activity of some brain limbic system regions after a memory task in adult male Wistar rats injected with scopolamine (1.0mg/kg, i.p.) was assessed using cytochrome oxidase (COx) histochemistry. The rats were trained following a working memory schedule in the MWM. A trained group injected with saline and an untreated control group were examined to compare changes in COx activity in the dorsal hippocampus, anterior thalamus, mammillary nuclei, prefrontal cortex and ventral tegmental area. The scopolamine-treated group showed an impairment of spatial learning. Also, a decrease in COx activity was found in this group as compared to the saline group in the anteroventral and anteromedial thalamic nuclei. Overall, these findings suggest that memory deficits induced by scopolamine may be due to impairment of the cholinergic function in the anterior thalamic nuclei.

Sexually dimorphic c-Fos expression following spatial working memory in young and adult rats.

The sex differences in the functional contribution of brain substrates were explored following acquisition of a spatial working memory task using quantification of c-Fos protein. Rats of both sexes were trained during adolescence and adulthood in Morris water maze using a hidden escape platform with different daily location. Two control groups for each sex and age were added to explore the c-Fos activation not specific to the memory process. These were a free-swimming group (yoked control) and a handled control (CO) group. Behaviorally, no age differences were found in number of days required by males to acquire the task, but females showed a delay in acquisition during adolescence (P30) that improved in adulthood (P90). Both sexes showed a learning-related increase in Fos immunoreactivity in the anterodorsal and anteroventral thalamus and medial and lateral mammillary nuclei during adolescence. Higher levels of learning-related Fos immunoreactivity were found in the infralimbic cortex, CA3 and CA1 only in females. During adulthood the common activated region was the prelimbic cortex with the addition of the infralimbic cortex in the male group and the lateral mammillary nucleus in the female group. These results indicated sex and age differences in brain functioning following working memory task. However, they could not be necessarily linked with differences in performance since similar results were found between males and females during adulthood. The activation of common and interrelated structures suggests that these structures are involved in spatial processing but it also highlights the relevance of developmental changes for understanding the memory process.

Basal and learning task-related brain oxidative metabolism in cirrhotic rats.

Hepatic encephalopathy is a neurological complication observed in patients with liver disease. Subjects with hepatic encephalopathy can develop memory alterations. In order to investigate brain oxidative metabolism in an animal model of chronic cirrhosis and its modification after spatial working memory task, we determined the neural metabolic activity of several brain limbic system regions by cytochrome oxidase (COx) histochemistry and assessed the spatial working memory in the Morris water maze of rats with cirrhosis by administration of thioacetamide. This COx histochemistry was done in cirrhotic and control rats under basal conditions and after the spatial working memory task. The histochemical results showed differences in basal COx activity between control and cirrhotic rats in hippocampal and thalamic regions. In cirrhotic rats basal COx activity was increased in the CA1 and CA3 areas of the hippocampus and reduced in the anterodorsal and anteroventral thalamic nuclei. We found impaired spatial working memory in animals with cirrhosis. These animals showed absence of metabolic activation of the CA3 hippocampal subfield and the lateral mammillary nucleus and disturbance of COx activity in the medial mammillary nucleus and the anteroventral thalamus. These findings suggest that cirrhotic rats show spatial working memory deficits that could be related to the alteration of metabolic activity of neural regions thought to be involved in the processing of spatial memories.

Induction of c-Fos expression in the mammillary bodies, anterior thalamus and dorsal hippocampus after fear conditioning.

The aim of the present study was to provide further evidence on the role of particular subdivisions of the mammillary bodies, anterior thalamus and dorsal hippocampus to contextual and auditory fear conditioning. We used c-Fos expression as a marker of neuronal activation to compare rats that received tone-footshock pairings in a distinctive context (conditioned group) to rats being exposed to both the context and the auditory CS without receiving footshocks (unconditioned group), and naïve rats that were only handled. Fos immunoreactivity was significantly increased only in the anterodorsal thalamic nucleus and the lateral mammillary nucleus of the conditioned group. However, the dorsal hippocampus showed the highest density of c-Fos positive nuclei in the naïve group as compared to the other groups. Together, our data support previous studies indicating a particular involvement of the mammillary bodies and anterior thalamus in fear conditioning.