When zero is not zero: the problem of ambiguous baseline conditions in fMRI
Open accessAbstract
By using blocked and rapid event-related functional MRI studies of memory, we explored the implications of using rest periods as a baseline condition in functional MRI studies. Activity in the medial temporal lobe (as well as in other brain regions) was substantially higher during rest than during several alternative baseline conditions. The effect of this elevated activity during rest was to reduce, eliminate, or even reverse the sign of the activity during task conditions relevant to memory functions. The results demonstrate that periods of rest are associated with significant cognitive activity and, therefore, provide a nonoptimal baseline for memory tasks. These results were observed not only when relatively long blocks of rest were used (experiment 1), but also when rest consisted of the short null trials typically used in rapid event-related designs (experiment 2). The findings have important implications for the design and interpretation of a wide range of fMRI studies of cognition.
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The distractor task was used as an active baseline with minimal recollection processes so that there was a baseline unlikely to include any sort of retrieval practice.
“This task was used as an active baseline with minimal recollection processes (Stark and Squire, 2001) so that there was a baseline that was unlikely to include any sort of retrieval practice.”
From Neural Correlates of Long-Term Memory Enhancement Following Retrieval Practice (2021) · cites this paper as Stark and Squire, 2001
We believe these results are a product of using an active baseline condition during data acquisition and may reflect the role of the supramarginal gyrus during arithmetic, language, and phonological processing tasks.
“We believe these results are a product of using an active baseline condition during data acquisition (Stark and Squire, 2001) and may reflect the role of the supramarginal gyrus during arithmetic, language, and phonological processing tasks (Hartwigsen et al., 2010; Evans et al., 2016).”
From Neural Correlates of Long-Term Memory Enhancement Following Retrieval Practice (2021) · cites this paper as Stark and Squire, 2001
Cites
Neurophysiological investigation of the basis of the fMRI signal
Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A. (2001) · Nature · doi:10.1038/35084005 · Cited by 6,542 · see citing works
Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space
Collins, D. L., Neelin, P., Peters, T. M., & Evans, A. C. (1994) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199403000-00005 · Cited by 3,431 · see citing works
Conceptual Processing during the Conscious Resting State: A Functional MRI Study
Binder, J. R., Frost, J. A., Hammeke, T. A., Bellgowan, P. S. F., Rao, S. M., & Cox, R. W. (1999) · Journal of Cognitive Neuroscience · doi:10.1162/089892999563265 · Cited by 1,066 · see citing works
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Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging
Fox, M. D., & Raichle, M. E. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2201 · Cited by 6,700 · see citing works
Functional connectivity in the resting brain: a network analysis of the default mode hypothesis
Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0135058100 · Cited by 6,358 · see citing works
Binder, J. R., Desai, R. H., Graves, W. W., & Conant, L. L. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp055 · Cited by 4,060 · see citing works
Squire, L. R., Stark, C. E. L., & Clark, R. E. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144130 · Cited by 2,680 · see citing works
Self-citationSpontaneous neuronal activity distinguishes human dorsal and ventral attention systems
Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L., & Raichle, M. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604187103 · Cited by 2,101 · see citing works
Eickhoff, S. B., Laird, A. R., Grefkes, C., Wang, L. E., Zilles, K., & Fox, P. T. (2009) · Human Brain Mapping · doi:10.1002/hbm.20718 · Cited by 1,924 · see citing works
Niendam, T. A., Laird, A. R., Ray, K. L., Dean, Y. M., Glahn, D. C., & Carter, C. S. (2012) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/s13415-011-0083-5 · Cited by 1,700 · see citing works
“However, the use of an active control Table 6 Brain regions (Brodmann areas in parentheses) with significant activation within healthy adults within the working memory condition is essential in order to isolate the cognitive process of interest in subtraction contrasts (Stark & Squire, 2001).”
BackgroundRaichle, M. E., & Mintun, M. A. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112819 · Cited by 1,630 · see citing works
Mind-wandering as spontaneous thought: a dynamic framework
Christoff, K., Irving, Z. C., Fox, K. C. R., Spreng, R. N., & Andrews-Hanna, J. R. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.113 · Cited by 1,376 · see citing works
Fransson, P. (2005) · Human Brain Mapping · doi:10.1002/hbm.20113 · Cited by 1,388 · see citing works
The functional neuroanatomy of autobiographical memory: a meta-analysis
Svoboda, E., McKinnon, M. C., & Levine, B. (2006) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2006.05.023 · Cited by 1,274 · see citing works
The Neural Basis of Inhibition in Cognitive Control
Aron, A. R. (2007) · The Neuroscientist · doi:10.1177/1073858407299288 · Cited by 1,098 · see citing works
Coherent spontaneous activity identifies a hippocampal-parietal memory network
Vincent, J. L., Snyder, A. Z., Fox, M. D., Shannon, B. J., Andrews, J. R., Raichle, M. E., & Buckner, R. L. (2006) · Journal of Neurophysiology · doi:10.1152/jn.00048.2006 · Cited by 959 · see citing works
Weissenbacher, A., Kasess, C., Gerstl, F., Lanzenberger, R., Moser, E., & Windischberger, C. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.005 · Cited by 776 · see citing works
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Szpunar, K. K., Watson, J. M., & McDermott, K. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610082104 · Cited by 784 · see citing works
Brain areas underlying visual mental imagery and visual perception: an fMRI study
Ganis, G., Thompson, W. L., & Kosslyn, S. M. (2004) · Cognitive Brain Research · doi:10.1016/j.cogbrainres.2004.02.012 · Cited by 765 · see citing works
Lindquist, K. A., Satpute, A. B., Wager, T. D., Weber, J., & Barrett, L. F. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhv001 · Cited by 713 · see citing works
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Andrews-Hanna, J. R., Reidler, J. S., Huang, C., & Buckner, R. L. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00830.2009 · Cited by 685 · see citing works
Evaluative and generative modes of thought during the creative process
Ellamil, M., Dobson, C., Beeman, M., & Christoff, K. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.08.008 · Cited by 611 · see citing works
Energetic basis of brain activity: implications for neuroimaging
Shulman, R. G., Rothman, D. L., Behar, K. L., & Hyder, F. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.06.005 · Cited by 590 · see citing works
Sleep transforms the cerebral trace of declarative memories
Gais, S., Albouy, G., Boly, M., Dang-Vu, T. T., Darsaud, A., Desseilles, M., Rauchs, G., Schabus, M., Sterpenich, V., Vandewalle, G., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705454104 · Cited by 412 · see citing works
Reindl, V., Gerloff, C., Scharke, W., & Konrad, K. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.05.060 · Cited by 411 · see citing works
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Daselaar, S. M., Fleck, M. S., Dobbins, I. G., Madden, D. J., & Cabeza, R. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhj112 · Cited by 392 · see citing works
Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., Ernst, J., Hell, D., Boeker, H., & Northoff, G. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2008.81 · Cited by 350 · see citing works
Golland, Y., Bentin, S., Gelbard, H., Benjamini, Y., Heller, R., Nir, Y., Hasson, U., & Malach, R. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhk030 · Cited by 337 · see citing works
Brotman, M. A., Rich, B. A., Guyer, A. E., Lunsford, J. R., Horsey, S. E., Reising, M. M., Thomas, L. A., Fromm, S. J., Towbin, K., Pine, D. S., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09010043 · Cited by 322 · see citing works
Singh, K. D., & Fawcett, I. P. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.01.051 · Cited by 312 · see citing works
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Spitsyna, G., Warren, J. E., Scott, S. K., Turkheimer, F. E., & Wise, R. J. S. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0559-06.2006 · Cited by 312 · see citing works
Mapping anterior temporal lobe language areas with fMRI: a multicenter normative study
Binder, J. R., Gross, W. L., Allendorfer, J. B., Bonilha, L., Chapin, J., Edwards, J. C., Grabowski, T. J., Langfitt, J. T., Loring, D. W., Lowe, M. J., et al. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.048 · Cited by 300 · see citing works
Power in Voxel-based lesion-symptom mapping
Kimberg, D. Y., Coslett, H. B., & Schwartz, M. F. (2007) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2007.19.7.1067 · Cited by 297 · see citing works
Walter, M., Henning, A., Grimm, S., Schulte, R. F., Beck, J., Dydak, U., Schnepf, B., Boeker, H., Boesiger, P., & Northoff, G. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.39 · Cited by 306 · see citing works
Kross, E., Davidson, M., Weber, J., & Ochsner, K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.019 · Cited by 295 · see citing works
Neuroimaging evidence for the emotional potency of odor-evoked memory
Herz, R. S., Eliassen, J., Beland, S., & Souza, T. (2004) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2003.08.009 · Cited by 265 · see citing works
Awake reactivation predicts memory in humans
Staresina, B. P., Alink, A., Kriegeskorte, N., & Henson, R. N. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1311989110 · Cited by 219 · see citing works
Episodic reinstatement in the medial temporal lobe
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Grimm, S., Schmidt, C. F., Bermpohl, F., Heinzel, A., Dahlem, Y., Wyss, M., Hell, D., Boesiger, P., Boeker, H., & Northoff, G. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.006 · Cited by 195 · see citing works
Ekstrom, A. D., Huffman, D. J., & Starrett, M. (2017) · Journal of Neurophysiology · doi:10.1152/jn.00531.2017 · Cited by 186 · see citing works
COURTNEY, S. M. (2004) · Cognitive, Affective, & Behavioral Neuroscience · doi:10.3758/cabn.4.4.501 · Cited by 198 · see citing works
Functional MRI in ADHD: a systematic literature review
Paloyelis, Y., Mehta, M. A., Kuntsi, J., & Asherson, P. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.10.1337 · Cited by 171 · see citing works
Gerlach, K. D., Spreng, R. N., Madore, K. P., & Schacter, D. L. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu001 · Cited by 148 · see citing works
Locus Coeruleus Activity Strengthens Prioritized Memories Under Arousal
Clewett, D. V., Huang, R., Velasco, R., Lee, T.-H., & Mather, M. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.2097-17.2017 · Cited by 152 · see citing works
The neural correlates of visual imagery: A co-ordinate-based meta-analysis
Winlove, C. I. P., Milton, F., Ranson, J., Fulford, J., MacKisack, M., Macpherson, F., & Zeman, A. (2018) · Cortex · doi:10.1016/j.cortex.2017.12.014 · Cited by 150 · see citing works
Dissociable networks involved in spatial and temporal order source retrieval
Ekstrom, A. D., Copara, M. S., Isham, E. A., Wang, W.-C., & Yonelinas, A. P. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.02.033 · Cited by 135 · see citing works
Krebs, R. M., Schott, B. H., & Düzel, E. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.019 · Cited by 129 · see citing works
Nonconscious formation and reactivation of semantic associations by way of the medial temporal lobe
Henke, K., Mondadori, C. R. A., Treyer, V., Nitsch, R. M., Buck, A., & Hock, C. (2003) · Neuropsychologia · doi:10.1016/s0028-3932(03)00035-6 · Cited by 128 · see citing works
Distinct brain systems underlie the processing of valence and arousal of affective pictures
Nielen, M. M. A., Heslenfeld, D. J., Heinen, K., Van Strien, J. W., Witter, M. P., Jonker, C., & Veltman, D. J. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.05.007 · Cited by 114 · see citing works
Cowan, E., Liu, A., Henin, S., Kothare, S., Devinsky, O., & Davachi, L. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1946-19.2020 · Cited by 97 · see citing works
Shifting visual perspective during retrieval shapes autobiographical memories
St. Jacques, P. L., Szpunar, K. K., & Schacter, D. L. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.028 · Cited by 108 · see citing works
Interoceptive awareness enhances neural activity during empathy
Ernst, J., Northoff, G., Böker, H., Seifritz, E., & Grimm, S. (2013) · Human Brain Mapping · doi:10.1002/hbm.22014 · Cited by 107 · see citing works
Neural systems supporting timing and chronometric counting: an FMRI study
Hinton, S. C., Harrington, D. L., Binder, J. R., Durgerian, S., & Rao, S. M. (2004) · Cognitive Brain Research · doi:10.1016/j.cogbrainres.2004.04.009 · Cited by 99 · see citing works
A neurocognitive model of meditation based on activation likelihood estimation (ALE) meta-analysis
Sperduti, M., Martinelli, P., & Piolino, P. (2012) · Consciousness and Cognition · doi:10.1016/j.concog.2011.09.019 · Cited by 87 · see citing works
Bellgowan, P. S. F., Bandettini, P. A., van Gelderen, P., Martin, A., & Bodurka, J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.08.042 · Cited by 84 · see citing works
Complementary roles of human hippocampal subregions during retrieval of spatiotemporal context
Copara, M. S., Hassan, A. S., Kyle, C. T., Libby, L. A., Ranganath, C., & Ekstrom, A. D. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.5341-13.2014 · Cited by 85 · see citing works
Pihlajamäki, M., & Sperling, R. A. (2009) · Behavioural Neurology · doi:10.1155/2009/276384 · Cited by 102 · see citing works
Zheng, L., Gao, Z., McAvan, A. S., Isham, E. A., & Ekstrom, A. D. (2021) · Nature Communications · doi:10.1038/s41467-021-26560-w · Cited by 54 · see citing works
Rubin-Falcone, H., Weber, J., Kishon, R., Ochsner, K., Delaparte, L., Doré, B., Zanderigo, F., Oquendo, M. A., Mann, J. J., & Miller, J. M. (2018) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2017.11.002 · Cited by 53 · see citing works
Zhang, H., Copara, M., & Ekstrom, A. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044886 · Cited by 50 · see citing works
Silvers, J. A., Hubbard, A. D., Chaudhury, S., Biggs, E., Shu, J., Grunebaum, M. F., Fertuck, E., Weber, J., Kober, H., Carson-Wong, A., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.06.020 · Cited by 30 · see citing works
Imaging the medial temporal lobe: exploring new dimensions
Brewer, J. B., & Moghekar, A. (2002) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(02)01881-8 · Cited by 26 · see citing works
Remembering and imagining differentially engage the hippocampus: a multivariate fMRI investigation
Kirwan, C. B., Ashby, S. R., & Nash, M. I. (2014) · Cognitive Neuroscience · doi:10.1080/17588928.2014.933203 · Cited by 19 · see citing works
Neural Correlates of Long-Term Memory Enhancement Following Retrieval Practice
Marin-Garcia, E., Mattfeld, A. T., & Gabrieli, J. D. E. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.584560 · Cited by 11 · see citing works
“We believe these results are a product of using an active baseline condition during data acquisition (Stark and Squire, 2001) and may reflect the role of the supramarginal gyrus during arithmetic, language, and phonological processing tasks (Hartwigsen et al., 2010; Evans et al., 2016).”
BackgroundMethod
- Authors
- Stark, C. E. L., & Squire, L. R.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Squire, Larry R.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-10-09
- Volume
- 98
- Issue
- 22
- Pages
- 12760-12766
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC60127
- OpenAlex
- W2105285178
- Cited by
- 724
- References
- 3
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 18 · 2023: 19 · 2022: 22 · 2021: 22 · 2020: 26 · 2019: 18 · 2018: 20 · 2017: 29 · 2016: 26 · 2015: 26 · 2014: 36 · 2013: 25 · 2012: 30
- FWCI
- 14.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (R37MH024600, MH12278, F32MH012278, R01MH024600, MH24600)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- baseline conditions, rest periods, memory, medial temporal lobe, blocked designs
- MeSH terms
- Adult, Cerebral Cortex, Cognition, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male
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