Stimulating brain tissue with bright light alters functional connectivity in brain at the resting state


Light is considered to modulate human brain function only via the retinal pathway, a way of thinking that we aimed to challenge in the present study. Literature provides evidence of inherent phototransduction for instance in the rat brain and there are potentially photosensitive opsin proteins like melanopsin and panopsin in the human brain too. In order to investigate a short term response, functional connectivity changes of the brain were studied in the resting state with functional magnetic resonance imaging during bright light stimulus via the ear canal. Lateral visual and sensorimotor networks showed increased functional connectivity in the light stimulus group compared to sham controls. The lateral visual network demonstrated slowly increasing functional connectivity on average and the same temporal characteristic was shared by diverse cerebellar brain regions. Hypothetical phototransduction signal pathways leading to responses in brain function are discussed as well as some observed effects and their possible link to the findings. Findings from this study together with the plausible photoreceptor candidates suggest that the brain possesses photosensitive properties, which will have interesting implications for the modulation of brain function and understanding the basic physiology of the brain.

Share and Cite:

Starck, T. , Nissilä, J. , Aunio, A. , Abou-Elseoud, A. , Remes, J. , Nikkinen, J. , Timonen, M. , Takala, T. , Tervonen, O. and Kiviniemi, V. (2012) Stimulating brain tissue with bright light alters functional connectivity in brain at the resting state. World Journal of Neuroscience, 2, 81-90. doi: 10.4236/wjns.2012.22012.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] [1] Vandewalle, G., Maquet, P. and Dijk, D.-J. (2009) Light as a modulator of cognitive brain function. Trends in Cognitive Sciences, 13, 429-438. doi:10.1016/j.tics.2009.07.004
[2] Campbell, S.S., Murphy, P.J. and Suhner, A.G. (2001) Extraocular phototransduction and circadian timing systems in vertebrates. Chronobiology International, 18, 137-172. doi:10.1081/CBI-100103183
[3] Peirson, S.N., Halford, S. and Foster, R.G. (2009) The evolution of irradiance detection: Melanopsin and the non-visual opsins. Philosophical Transactions of the Royal Society B: Biological Sciences, 364, 2849-2865. doi:10.1098/rstb.2009.0050
[4] Berson, D.M., Dunn, F.A. and Takao, M. (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science, 295, 1070-1073. doi:10.1126/science.1067262
[5] Terakita, A. (2005) The opsins. Genome Biology, 6, 213. doi:10.1186/gb-2005-6-3-213
[6] Halford, S., Freedman, M.S., Bellingham, J., Inglis, S.L., Poopalasundaram, S., Soni, B.G., Foster, R.G. and Hunt, D.M. (2001) Characterization of a novel human opsin gene with wide tissue expression and identification of embedded and flanking genes on chromosome 1q43. Genomics, 72, 203-208. doi:10.1006/geno.2001.6469
[7] Mitsui, S., Tsuruoka, N., Yamashiro, K., Nakazato, H. and Yamaguchi, N. (1999) A novel form of human neuropsin, a brain-related serine protease, is generated by alternative splicing and is expressed preferentially in human adult brain. European Journal of Biochemistry, 260, 627-634. doi:10.1046/j.1432-1327.1999.00213.x
[8] Tarttelin, E.E., Bellingham, J., Hankins, M.W., Foster, R.G. and Lucas, R.J. (2003) Neuropsin (opn5): A novel opsin identified in mammalian neural tissue. FEBS Letters, 554, 410-416. doi:10.1016/S0014-5793(03)01212-2
[9] Nakane, Y., Ikegami, K., Ono, H., Yamamoto, N., Yoshida, S., Hirunagi, K., Ebihara, S., Kubo, Y. and Yoshimura, T. (2010) A mammalian neural tissue opsin (opsin 5) is a deep brain photoreceptor in birds. Proceedings of the National Academy of Sciences of the United States of America, 107, 15264-15268. doi:10.1073/pnas.1006393107
[10] White, J.H., Chiano, M., Wigglesworth, M., Geske, R., Riley, J., White, N., Hall, S., Zhu, G., Maurio, F., Savage, T., Anderson, W., Cordy, J., Ducceschi, M., GAIN investigators, Vestbo, J. and Pillai, S.G. (2008) Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation. Human Molecular Genetics, 17, 1890-1903. doi:10.1093/hmg/ddn087
[11] BrainSpan: Atlas of the Developing Human Brain [Internet]. Funded by ARRA Awards 1RC2MH089921-01, 1RC2MH090047-01, and 1RC2MH089929-01. ?2011. Accessed 31 March 2011.
[12] Nissil?, J., M?ntt?ri, S., Tuominen, H., S?rkioja, T., Timonen, M. and Saarela, S. (2011a) The Abundance and Distribution of Encephalopsin (OPN3) Protein in Mouse Brain. Proceedings of the Scandinavian Physiological Society, Unpublished.
[13] Nissil?, J., M?ntt?ri, S., Tuominen, H., S?rkioja, T., Timonen, M. and Saarela, S. (2011b) The Abundance and Distribution of Encephalopsin (OPN3) Protein in Human Brain. Proceedings of the Scandinavian Physiological Society, Unpublished.
[14] Wade, P.D., Taylor, J. and Siekevitz, P. (1988) Mammalian cerebral cortical tissue responds to low-intensity visible light. Proceedings of the National Academy of Sciences of the United States of America, 85, 9322-9326. doi:10.1073/pnas.85.23.9322
[15] Leszkiewicz, D.N., Kandler, K. and Aizenman, E. (2000) Enhancement of nmda receptor-mediated currents by light in rat neurones in vitro. Journal of Physiology, 524, 365-374. doi:10.1111/j.1469-7793.2000.t01-1-00365.x
[16] Nieto, P.S., Valdez, D.J., Acosta-Rodr?guez, V.A. and Guido, M.E. (2011) Expression of Novel Opsins and Intrinsic Light Responses in the Mammalian Retinal Ganglion Cell Line RGC-5. Presence of OPN5 in the Rat Retina. PLoS One, 5, e26417. doi:10.1371/journal.pone.0026417
[17] Golden, R.N., Gaynes, B.N., Ekstrom, R.D., Hamer, R.M., Jacobsen, F.M., Suppes, T., Wisner, K.L. and Nemeroff, C.B. (2005) The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence. American Journal of Psychiatry, 162, 656-662. doi:10.1176/appi.ajp.162.4.656
[18] Van Brunt, E.E., Shepherd, M.D., Wall, J.R., Ganong, W.F. and Clegg, M.T. (1964) Penetration of light into the brain of mammals. Annals of the New York Academy of Sciences, 117, 217-214. doi:10.1111/j.1749-6632.1964.tb48177.x
[19] Moan, J. (2001) Visible light and UV radiation. In: Brune, D., Ed., Radiation at Home, Outdoors and in the Workplace, Scandinavian Science Publisher.
[20] Ugryumova, N., Matcher, S.J. and Attenburrow, D.P. (2004) Measurement of bone mineral density via light scattering. Physics in Medicine and Biology, 49, 469-483. doi:10.1111/j.1749-6632.1964.tb48177.x
[21] Timonen, M., Nissil?, J., Liettu, A., Jokelainen, J., Jurvelin, H., Aunio, A., R?s?nen, P. and Takala, T. (2012) Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? A pilot study. Medical Hypotheses, in press. doi:10.1016/j.mehy.2012.01.019
[22] Jurvelin, H., Nissil?, J., Timonen, M., Takala, T., Jokelainen, J. and R?s?nen, P. (2012) Transcranial bright light treatment via ear canals in seasonal affective disorder (SAD)—A randomized controlled trial. Unpublished.
[23] Logothetis, N.K. and Wandell, B.A. (2004) Interpreting the bold signal. Annual Review of Physiology, 66, 735-769. doi:10.1146/annurev.physiol.66.082602.092845
[24] Biswal, B., Yetkin, F.Z., Haughton, V.M. and Hyde, J.S. (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic Resonance in Medicine, 34, 537-541. doi:10.1002/mrm.1910340409
[25] Fornito, A. and Bullmore, E.T. (2010) What can spontaneous fluctuations of the blood oxygenation-level-dependent signal tell us about psychiatric disorders? Current Opinion in Psychiatry, 23, 239-249. doi:10.1097/YCO.0b013e328337d78d
[26] Yan, L., Zhuo, Y., Ye, Y., Xie, S. X., An, J., Aguirre, G. K. and Wang, J. (2009) Physiological origin of low-frequency drift in blood oxygen level dependent (bold) functional magnetic resonance imaging (fMRI). Magnetic Resonance in Medicine, 61, 819-827. doi:10.1002/mrm.21902
[27] Bruhn, H., Fransson, P. and Frahm, J. (2001) Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation. Journal of Magnetic Resonance Imaging, 13, 325-334. doi:10.1002/jmri.1047
[28] Schmidt, K.F., Febo, M., Shen, Q., Luo, F., Sicard, K.M., Ferris, C.F., Stein, E.A. and Duong, T.Q. (2006) Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional mri. Psychopharmacology (Berlin), 185, 479-486. doi:10.1007/s00213-006-0319-1
[29] Beckmann C., Mackay C., Filippini N. and Smith S. (2009). Group comparison of resting-state fMRI data using multi-subject ICA and dual regression. Neuroimage, 47, S148. doi:10.1016/S1053-8119(09)71511-3
[30] Calhoun, V.D., Pekar, J.J. and Pearlson, G.D. (2004) Alcohol intoxication effects on simulated driving: Exploring alcohol-dose effects on brain activation using functional MRI. Neuropsychopharmacoloy, 29, 2097-2107. doi:10.1073/pnas.0811879106
[31] Zuo, X.-N., Kelly, C., Adelstein, J.S., Klein, D.F., Castellanos, F.X. and Milham, M.P. (2010) Reliable intrinsic connectivity networks: Test-retest evaluation using ICA and dual regression approach. Neuroimage, 49, 2163-2177. doi:10.1016/j.neuroimage.2009.10.080
[32] Beckmann, C.F. and Smith, S.M. (2004) Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Transactions on Medical Imaging, 23, 137-152. doi:10.1109/TMI.2003.822821
[33] Jenkinson, M., Bannister, P., Brady, M. and Smith, S. (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage, 17, 825-841. doi:10.1006/nimg.2002.1132
[34] Smith, S.M. (2002) Fast robust automated brain extraction. Human Brain Mapping, 17, 143-155. doi:10.1002/hbm.10062
[35] Jenkinson, M. and Smith, S. (2001) A global optimisation method for robust affine registration of brain images. Medical Image Analysis, 5, 143-156. doi:10.1016/S1361-8415(01)00036-6
[36] Aguirre, G.K., Zarahn, E. and D’Esposito, M. (1997). Empirical analyses of bold fmri statistics. ii. spatially smoothed data collected under null-hypothesis and experimental conditions. Neuroimage, 5, 199-212. doi:10.1006/nimg.1997.0264
[37] Wang, J., Wang, Z., Aguirre, G.K. and Detre, J.A. (2005) To smooth or not to smooth? Roc analysis of perfusion fmri data. Magnetic Resonance Imaging, 23, 75-81. doi:10.1016/j.mri.2004.11.009
[38] Nichols, T.E. and Holmes, A.P. (2002) Nonparametric permutation tests for functional neuroimaging: A primer with examples. Human Brain Mapping, 15, 1-25. doi:10.1002/hbm.1058
[39] Smith, S.M., Nichols, T. E., 2009. Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage, 44, 83-98. doi:10.1016/j.neuroimage.2008.03.061
[40] DeArmond, S.J., Fusco, M.M. and Dewey, M.M. (1989) Structure of the human brain (3rd edition). Oxford University Press, Oxford.
[41] Blackshaw, S. and Snyder, S.H. (1999) Encephalopsin: A novel mammalian extraretinal opsin discretely localized in the brain. Journal of Neuroscience, 19, 3681-3690.
[42] Rowland, N.C., Goldberg, J.A. and Jaeger, D. (2010) Cortico-cerebellar coherence and causal connectivity during slowwave activity. Neuroscience, 166, 698-711. doi:10.1016/j.neuroscience.2009.12.048
[43] Buzsáki, G., Kaila, K. and Raichle, M. (2007) Inhibition and brain work. Neuron, 56, 771-783. doi:10.1016/j.neuron.2007.11.008
[44] Logothetis, N.K. (2008) What we can do and what we cannot do with fMRI. Nature, 453, 869-878. doi:10.1038/nature06976
[45] Steriade, M. (1996) Arousal: Revisiting the reticular activating system. Science, 272, 225-226. doi:10.1126/science.272.5259.225
[46] Ungerleider, L.G. and Mishkin, M. (1982) Two cortical systems. In: Ingle, D.J., Goodale, M.A. and Mansfield, R.J.W., Eds., Analysis of Visual Behavior, MIT Press, Cambridge.
[47] Perrin, F., Peigneux, P., Fuchs, S., Verhaeghe, S., Laureys, S., Middleton, B., Degueldre, C., Del Fiore, G., Vandewalle, G., Balteau, E., Poirrier, R., Moreau, V., Luxen, A., Maquet, P. and Dijk, D.J. (2004) Nonvisual responses to light exposure in the human brain during the circadian night. Current Biology, 14, 1842-1846. doi:10.1016/j.cub.2004.09.082
[48] Stoodley, C.J. and Schmahmann, J.D. (2009) Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies. Neuroimage, 44, 489-501. doi:10.1016/j.neuroimage.2008.08.039

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.