Skip to main content
Log in

Prolonged fasting impairs neural reactivity to visual stimulation

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Amunts K, Malikovic A, Mohlberg H, Schormann T, Zilles K (2000) Brodmann’s areas 17 and 18 brought into stereotaxic space-where and how variable? Neuroimage 11:66–84. Available at: http://www.sciencedirect.com/science/article/pii/S1053811999905165. Accessed 23 Jan 2014

  • Anderson AW, Heptulla RA, Driesen N, Flanagan D, Goldberg PA, Jones TW, Rife F, Sarofin H, Tamborlane W, Sherwin R et al (2006) Effects of hypoglycemia on human brain activation measured with fMRI. Magn Reson Imaging 24:693–697

    Article  CAS  PubMed  Google Scholar 

  • Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839–851. Available at: 10.1016/j.neuroimage.2005.02.018. Accessed 22 May 2013

  • Beckmann CF, Smith SM (2004) Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Trans Med Imaging 23:137–52. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14964560. Accessed 20 Jan 2014

  • Beckmann CF, Smith SM (2005) Tensorial extensions of independent component analysis for multisubject FMRI analysis. Neuroimage 25:294–311. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15734364. Accessed 6 Nov 2012

  • Booth JR, Burman DD, Meyer JR, Trommer BL, Davenport ND, Parrish TB, Gitelman DR, Mesulam MM (2004) Brain-behavior correlation in children depends on the neurocognitive network. Human Brain Mapping 23:99–108. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2638501&tool=pmcentrez&rendertype=abstract. Accessed 20 Dec 2013

  • Brewer */*AA, Barton B (2012) “Visual Field Map Organization in Human Visual Cortex,” in visual cortex—current status and perspectives (eds) S. Molotchnikoff and J. Rouat (InTech), 29–60

  • Calhoun VD, Altschul D, McGinty V, Shih R, Scott D, Sears E, Pearlson GD (2004) Alcohol intoxication effects on visual perception: an fMRI study. Human Brain Mapping 21:15–26. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14689506. Accessed 11 Dec 2013

  • Carp J, Park J, Polk Ta, Park DC (2011) Age differences in neural distinctiveness revealed by multi-voxel pattern analysis. Neuroimage 56:736–43. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2962693&tool=pmcentrez&rendertype=abstract. Accessed 20 Dec 2013

  • Chambers ES, Bridge MW, Jones DA (2009) Carbohydrate sensing in the human mouth: effects on exercise performance and brain activity. J Physiol 587:1779–94. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2683964&tool=pmcentrez&rendertype=abstract. Accessed 13 June 2013

  • Ciesielski KT, Lesnik PG, Savoy RL, Grant EP, Ahlfors SP (2006) Developmental neural networks in children performing a Categorical N-Back Task. NeuroImage 33:980–90. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16997580. Accessed 18 Dec 2013

  • Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nature Rev. Neurosci 3:201–15. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11994752. Accessed 11 Dec 2013

  • Dai X-J, Gong H-H, Wang Y-X, Zhou F-Q, Min Y-J, Zhao F, Wang S-Y, Liu B-X, Xiao X-Z (2012) Gender differences in brain regional homogeneity of healthy subjects after normal sleep and after sleep deprivation: a resting-state fMRI study. Sleep Med 13:720–7. Available at: http://www.sciencedirect.com/science/article/pii/S1389945712001104. Accessed 17 March 2014

  • Dale AM, Buckner RL (1997) Selective averaging of rapidly presented individual trials using fMRI. Human Brain Mapping 5:329–40. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20408237

  • Dichter GS, Felder JN, Petty C, Bizzell J, Ernst M, Smoski MJ (2009) The effects of psychotherapy on neural responses to rewards in major depression. Biol Psychiatry 66:886–97. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3657763&tool=pmcentrez&rendertype=abstract. Accessed 20 Dec 2013

  • Driesen NR, Goldberg PA, Anderson AW, Tang L, Flanagan DE, Sherwin RS, Gore JC (2007) Hypoglycemia reduces the blood-oxygenation level dependent signal in primary auditory and visual cortex: a functional magnetic resonance imaging study. J Neurosci Res 85:575–582

    Article  CAS  PubMed  Google Scholar 

  • Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25:1325–1335

    Article  PubMed  Google Scholar 

  • Falkenberg I, Kohn N, Schoepker R, Habel U (2012) Mood induction in depressive patients: a comparative multidimensional approach. PloS One 7(1):e30016. doi:10.1371/journal.pone.0030016

  • Fernández-Seara Ma, Mengual E, Vidorreta M, Aznárez-Sanado M, Loayza FR, Villagra F, Irigoyen J, Pastor Ma (2012). Cortical hypoperfusion in Parkinson’s disease assessed using arterial spin labeled perfusion MRI. Neuroimage 59:2743–2750. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22032942. Accessed 20 Dec 2013

  • Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711

    Article  CAS  PubMed  Google Scholar 

  • Fox P, Raichle M, Mintun M, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–464. Available at: http://www.sciencemag.org/content/241/4864/462.abstract. Accessed 5 June 2013

  • Goodale Ma, Milner AD (1992) Separate visual pathways for perception and action. Trends Neurosci 15:20–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1374953

  • Green MW, Elliman NA, Rogers PJ (1997) Impaired cognitive processing in dieters: failure of attention focus or resource capacity limitation? British J Health Psychol 2, 259–267. Available at: 10.1111/j.2044-8287.1997.tb00540.x. Accessed 13 Dec 2013

  • Harsay Ha, Cohen MX, Oosterhof NN, Forstmann BU, Mars RB, Ridderinkhof KR (2011) Functional connectivity of the striatum links motivation to action control in humans. J Neurosci Off J Soc Neurosci 31:10701–11. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21775613. Accessed 13 Dec 2013

  • Herzog N, Jauch-Chara K, Hyzy F, Richter A, Friedrich A, Benedict C, Oltmanns KM (2013) Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men. Psychoneuroendocrinology 38:2075–82. Available at: http://www.sciencedirect.com/science/article/pii/S0306453013001133. Accessed 7 Mar 2014

  • Hojlund K, Wildner-Christensen M, Eshoj O, Skjarbak C, Holst JJ, Koldkjar O, Moller Jensen D, Beck-Nielsen H (2001) Reference intervals for glucose, {beta}-cell polypeptides, and counterregulatory factors during prolonged fasting. Am J Physiol Endocrinol Metab 280:E50–e58. Available at: http://ajpendo.physiology.org/content/280/1/E50. Accessed 14 Nov 2013

  • Hutcherson CA, Goldin PR, Ochsner KN, Gabrieli JDE, Barrett LF, Gross JJ (2005) Attention and emotion: does rating emotion alter neural responses to amusing and sad films? Neuroimage 27:656–668

    Article  CAS  PubMed  Google Scholar 

  • Hyvärinen A (1999) Fast and robust fixed-point algorithms for independent component analysis. IEEE Trans Neural Networks/Publ IEEE Neural Networks Council 10:626–34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18252563. Accessed 20 Jan 2014

  • Hoptman MJ, Zuo X-N, Butler PD, Javitt, DC, D’Angelo D, Mauro CJ, Milham MP (2010) Amplitude of low-frequency oscillations in schizophrenia: a resting state fMRI study. Schizophr Res 117:13–20. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2822110&tool=pmcentrez&rendertype=abstract. Accessed 18 Dec 2013

  • Jiang G, Zhang BB (2003) Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 284:E671–E678. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12626323. Accessed 22 May 2013

  • Kensinger Ea, Addis DR, Atapattu RK (2011) Amygdala activity at encoding corresponds with memory vividness and with memory for select episodic details. Neuropsychologia 49:663–73. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3060942&tool=pmcentrez&rendertype=abstract. Accessed 19 Dec 2013

  • Kim C, Cilles SE, Johnson NF, Gold BT (2012) Domain general and domain preferential brain regions associated with different types of task switching: a meta-analysis. Human Brain Mapping 33:130–42. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3421461&tool=pmcentrez&rendertype=abstract. Accessed 20 Dec 2013

  • Kohn N, Falkenberg I, Kellermann T, Eickhoff SB, Gur RC, Habel U (2013) Neural correlates of effective and ineffective mood induction. Soc Cogn Affect Neurosci. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23576810

  • Kujovic M, Zilles K, Malikovic A, Schleicher A, Mohlberg H, Rottschy C, Eickhoff SB, Amunts K (2013) Cytoarchitectonic mapping of the human dorsal extrastriate cortex. Brain Structure Funct 218:157–72. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3535362&tool=pmcentrez&rendertype=abstract. Accessed 4 Mar 2014

  • Madden DJ, Costello MC, Dennis Na, Davis SW, Shepler AM, Spaniol J, Bucur B, Cabeza R (2010) Adult age differences in functional connectivity during executive control. Neuroimage 52:643–57. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2902259&tool=pmcentrez&rendertype=abstract. Accessed 20 Dec 2013

  • Malikovic A, Amunts K, Schleicher A, Mohlberg H, Eickhoff SB, Wilms M, Palomero-Gallagher N, Armstrong E, Zilles K (2007) Cytoarchitectonic analysis of the human extrastriate cortex in the region of V5/MT+: a probabilistic, stereotaxic map of area hOc5. Cerebral cortex (New York: 1991) 17:562–574. Available at: http://cercor.oxfordjournals.org/content/17/3/562.full. Accessed 12 Feb 2014

  • Martínez a Anllo-Vento L, Sereno MI, Frank LR, Buxton RB, Dubowitz DJ, Wong EC, Hinrichs H, Heinze HJ, Hillyard Sa (1999) Involvement of striate and extrastriate visual cortical areas in spatial attention. Nature Neurosci 2:364–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10204544

  • Metzak P, Feredoes E, Takane Y, Wang L, Weinstein S, Cairo T, Ngan ETC, Woodward TS (2011) Constrained principal component analysis reveals functionally connected load-dependent networks involved in multiple stages of working memory. Human Brain Mapping 32:856–871. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20572208. Accessed 12 Dec 2013

  • Moratti S, Keil A (2009) Not what you expect: experience but not expectancy predicts conditioned responses in human visual and supplementary cortex. Cerebral cortex (New York: 1991) 19:2803–2809. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19304914. Accessed 20 Dec 2013

  • Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9:97–113. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5146491

  • Patriat R, Molloy EK, Meier TB, Kirk GR, Nair Va, Meyerand ME, Prabhakaran V, Birn RM (2013) The effect of resting condition on resting-state fMRI reliability and consistency: a comparison between resting with eyes open, closed, and fixated. Neuroimage 78:463–473. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23597935. Accessed 13 Jan 2014

  • Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D (2010) Cerebral blood flow response to functional activation. J Cerebral Blood Flow Metab: Official J Int Soc Cerebral Blood Flow Metab 30:2–14. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2872188&tool=pmcentrez&rendertype=abstract. Accessed 6 June 2013

  • Peiffer AM, Hugenschmidt CE, Maldjian Ja, Casanova R, Srikanth R, Hayasaka S, Burdette JH, Kraft Ra, Laurienti PJ (2009) Aging and the interaction of sensory cortical function and structure. Human Brain Mapping 30:228–40. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18072271. Accessed 19 Dec 2013

  • Pellerin L (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc National Acad Sci 91:10625–10629. Available at: http://www.pnas.org/content/91/22/10625.short. Accessed 5 June 2013

  • Riccio CA, Reynolds CR, Lowe P, Moore JJ (2002) The continuous performance test: a window on the neural substrates for attention? Arch Clin Neuropsychol 17(3):235–272. doi:10.1016/S0887-6177(01)00111-1

  • Schafer RJ, Page KA, Arora J, Sherwin R, Constable RT (2012) BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent. Brain Lang 120:1–14. Available at: 10.1016/j.bandl.2011.07.003. Accessed 5 June 2013

  • Schneider F, Gur RC, Gur RE, Muenz LR (1994) Standardized mood induction with happy and sad facial expressions. Psychiatry Res 51:19–31. Available at:<Go to ISI>://A1994MZ41800003

  • Schöpf V, Fischmeister FPS, Windischberger C, Gerstl F, Wolzt M, Karlsson KAE, Moser E (2013) Effects of individual glucose levels on the neuronal correlates of emotions. Frontiers Human Neurosci 7. Available at: http://www.frontiersin.org/Human_Neuroscience/10.3389/fnhum.2013.00212/full. Accessed 27 May 2013

  • Schott BH, Niehaus L, Wittmann BC, Schütze H, Seidenbecher CI, Heinze H-J, Düzel E (2007) Ageing and early-stage Parkinson’s disease affect separable neural mechanisms of mesolimbic reward processing. Brain: J Neurol 130:2412–2424. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17626038. Accessed 17 Dec 2013

  • Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18501637. Accessed 10 Jan 2014

  • Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR et al (2009) Correspondence of the brain’s functional architecture during activation and rest. Proceedings National Acad Sci USA 106:13040–13045. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2722273&tool=pmcentrez&rendertype=abstract. Accessed 23 Aug 2012

  • Southgate DA (1995) Digestion and metabolism of sugars. Am J Clin Nutr 62:203S–210S, discussion 211S. Available at: http://ajcn.nutrition.org/content/62/1/203S.abstract. Accessed 5 June 2013

  • Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–89. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11771995. Accessed 11 Dec 2013

  • Vanni S, Tanskanen T, Seppä M, Uutela K, Hari R (2001) Coinciding early activation of the human primary visual cortex and anteromedial cuneus. Proc National Acad Sci USA 98:2776–80. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=30215&tool=pmcentrez&rendertype=abstract

  • Warren RE, Frier BM (2005) Hypoglycaemia and cognitive function. Diabetes Obesity Metab 7:493–503. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16050942. Accessed 5 June 2013

  • Warren RE, Sommerfield AJ, Greve A, Allen KV, Deary IJ, Frier BM (2008) Moderate hypoglycaemia after learning does not affect memory consolidation and brain activation during recognition in non-diabetic adults. Diabetes/Metabolism Research And Reviews 24, 247–52. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18088081. Accessed 5 June 2013

  • Wittchen HU, Wunderlich U, Gruschwitz S, Zaudig M (1997) Strukturiertes Klinisches interview für DSM-IV. Hogrefe, Göttingen

    Google Scholar 

Download references

Acknowledgments

This work was supported by the Faculty of Medicine, RWTH Aachen University (START program 138/09) and by the German Research Foundation (DFG, IRTG 1328, International Research Training Group). UH is supported by a grant from the IZKF Aachen (Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, N4-4). We thank the IZKF Aachen (David Weyer, Andre Schüppen) for technical support. This work is also subject to the medical doctoral thesis of AW.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. Kohn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kohn, N., Wassenberg, A., Toygar, T. et al. Prolonged fasting impairs neural reactivity to visual stimulation. Brain Struct Funct 221, 147–158 (2016). https://doi.org/10.1007/s00429-014-0898-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-014-0898-2

Keywords

Navigation