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      Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer’s Disease

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          Abstract

          Background: Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain. Objective: We assessed whether transcranial photobiomodulation with near-infrared light modulates cerebral electrical activity through electroencephalogram (EEG) and cerebral blood flow (CBF). Methods: We conducted a single-blind, sham-controlled pilot study to test the effect of continuous (c-tPBM), pulse (p-tPBM), and sham (s-tPBM) transcranial photobiomodulation on EEG oscillations and CBF using diffuse correlation spectroscopy (DCS) in a sample of ten healthy subjects [6F/4 M; mean age 28.6±12.9 years]. c-tPBM near-infrared radiation (NIR) (830 nm; 54.8 mW/cm2; 65.8 J/cm2; 2.3 kJ) and p-tPBM (830 nm; 10 Hz; 54.8 mW/cm2; 33%; 21.7 J/cm2; 0.8 kJ) were delivered concurrently to the frontal areas by four LED clusters. EEG and DCS recordings were performed weekly before, during, and after each tPBM session. Results: c-tPBM significantly boosted gamma (t = 3.02, df = 7, p < 0.02) and beta (t = 2.91, df = 7, p < 0.03) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with a widespread increase over frontal-central scalp regions. There was no significant effect of tPBM on CBF compared to sham. Conclusion: Our data suggest a dose-dependent effect of tPBM with NIR on cerebral gamma and beta neuronal activity. Altogether, our findings support the neuromodulatory effect of transcranial NIR.

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          Most cited references73

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          Mechanisms of gamma oscillations.

          Gamma rhythms are commonly observed in many brain regions during both waking and sleep states, yet their functions and mechanisms remain a matter of debate. Here we review the cellular and synaptic mechanisms underlying gamma oscillations and outline empirical questions and controversial conceptual issues. Our main points are as follows: First, gamma-band rhythmogenesis is inextricably tied to perisomatic inhibition. Second, gamma oscillations are short-lived and typically emerge from the coordinated interaction of excitation and inhibition, which can be detected as local field potentials. Third, gamma rhythm typically concurs with irregular firing of single neurons, and the network frequency of gamma oscillations varies extensively depending on the underlying mechanism. To document gamma oscillations, efforts should be made to distinguish them from mere increases of gamma-band power and/or increased spiking activity. Fourth, the magnitude of gamma oscillation is modulated by slower rhythms. Such cross-frequency coupling may serve to couple active patches of cortical circuits. Because of their ubiquitous nature and strong correlation with the "operational modes" of local circuits, gamma oscillations continue to provide important clues about neuronal population dynamics in health and disease.
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            Gamma frequency entrainment attenuates amyloid load and modifies microglia.

            Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1-40 and Aβ 1-42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ1-40 and Aβ1-42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
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              Oscillatory gamma activity in humans and its role in object representation.

              We experience objects as whole, complete entities irrespective of whether they are perceived by our sensory systems or are recalled from memory. However, it is also known that many of the properties of objects are encoded and processed in different areas of the brain. How then, do coherent representations emerge? One theory suggests that rhythmic synchronization of neural discharges in the gamma band (around 40 Hz) may provide the necessary spatial and temporal links that bind together the processing in different brain areas to build a coherent percept. In this article we propose that this mechanism could also be used more generally for the construction of object representations that are driven by sensory input or internal, top-down processes. The review will focus on the literature on gamma oscillatory activities in humans and will describe the different types of gamma responses and how to analyze them. Converging evidence that suggests that one particular type of gamma activity (induced gamma activity) is observed during the construction of an object representation will be discussed.
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                Author and article information

                Journal
                Journal of Alzheimer's Disease
                JAD
                IOS Press
                13872877
                18758908
                October 12 2021
                October 12 2021
                : 83
                : 4
                : 1481-1498
                Affiliations
                [1 ]Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
                [2 ]Department of Clinical Experimental Medicine, Psychiatric Unit, University of Pisa, Pisa, Italy
                [3 ]HMS/MGH Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
                [4 ]Department of Psychiatry, Harvard Medical School, Boston, MA, USA
                [5 ]School for Social Work, Smith College, Northampton, MA, USA
                [6 ]Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
                [7 ]LiteCure LLC, New Castle, DE, USA
                [8 ]Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
                [9 ]Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
                Article
                10.3233/JAD-210058
                34092636
                8374b5dd-c6db-41a9-9874-44031d81e39f
                © 2021
                History

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