Reduced Orbitofrontal and Parietal Gray Matter in Chronic Insomnia: A Voxel-Based Morphometric Study
Abstract
Background Brain mechanisms of chronic insomnia, a highly prevalent condition, have barely been investigated. We demonstrate here a decrease in orbitofrontal gray matter (GM) volume that strongly correlates with the severity of complaints.Methods In a case-control study, optimized voxel-based morphometry was used to compare the regional brain volumes of 24 medication-free chronic primary insomnia patients (age range 52-74 years, 17 women), carefully selected to exclude psychiatric comorbidity, with those of 13 matched control subjects without sleep problems (age range 50-76 years, 9 women). Additionally, the correlation of regional volumes with insomnia severity was investigated.Results Patients had a smaller volume of GM in the left orbitofrontal cortex, strongly correlating (r = -.71) with the subjective severity of insomnia. Furthermore, reduced GM volume was found in the anterior and posterior precuneus. Patients did not show increased GM volume in any area. No group differences were found for white matter volume.Conclusions This is the first voxel-based morphometry study showing structural brain correlates of insomnia and their relation with insomnia severity. Functional roles of the affected areas in decision-making and stimulus processing might better guide future research into the poorly understood condition of insomnia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The severity of sleep complaints in insomnia patients correlated with structural abnormalities in the part of the orbitofrontal cortex that is essential for the evaluation of comfort.
“Interestingly, these observations were recently supported by our finding [5] that the severity of their sleep complaints correlated with structural abnormalities in the part of the orbitofrontal cortex that is essential for the evaluation of comfort [27, 73].”
From Sleep, vigilance, and thermosensitivity (2012) · cites this paper as [5]
Cites
Voxel-Based Morphometry—The Methods
Ashburner, J., & Friston, K. J. (2000) · NeuroImage · doi:10.1006/nimg.2000.0582 · Cited by 8,676 · see citing works
The precuneus: a review of its functional anatomy and behavioural correlates
Cavanna, A. E., & Trimble, M. R. (2006) · Brain · doi:10.1093/brain/awl004 · Cited by 5,128 · see citing works
Emotion, Decision Making and the Orbitofrontal Cortex
Bechara, A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.295 · Cited by 3,589 · see citing works
Voxel-based morphometry of the human brain: Methods and applications
Mechelli, A., Price, C., Friston, K. J., & Ashburner, J. (2005) · Current Medical Imaging Formerly Current Medical Imaging Reviews · doi:10.2174/1573405054038726 · Cited by 928 · see citing works
Functional Neuroimaging Evidence for Hyperarousal in Insomnia
Nofzinger, E. A., Buysse, D. J., Germain, A., Price, J. C., Miewald, J. M., & Kupfer, D. J. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.2126 · Cited by 752 · see citing works
Reduced volume of orbitofrontal cortex in major depression
Bremner, J. D., Vythilingam, M., Vermetten, E., Nazeer, A., Adil, J., Khan, S., Staib, L. H., & Charney, D. S. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01336-1 · Cited by 537 · see citing works
Quantitative criteria for insomnia
Lichstein, K. L., Durrence, H. H., Taylor, D. J., Bush, A. J., & Riedel, B. W. (2003) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(02)00023-2 · Cited by 531 · see citing works
Fukunaga, M., Horovitz, S. G., van Gelderen, P., de Zwart, J. A., Jansma, J. M., Ikonomidou, V. N., Chu, R., Deckers, R., Leopold, D. A., & Duyn, J. H. (2006) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2006.04.018 · Cited by 365 · see citing works
Venkatraman, V., Chuah, Y. L., Huettel, S. A., & Chee, M. W. (2007) · SLEEP · doi:10.1093/sleep/30.5.603 · Cited by 359 · see citing works
The Role of the Orbitofrontal Cortex in Anxiety Disorders
Milad, M. R., & Rauch, S. L. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1401.006 · Cited by 313 · see citing works
LeBlanc, M., Beaulieu‐Bonneau, S., Mérette, C., Savard, J., Ivers, H., & Morin, C. M. (2007) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2007.03.004 · Cited by 308 · see citing works
Wicklow, A. A., & Espie, C. A. (2000) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(99)00136-9 · Cited by 282 · see citing works
Prefrontal Hypoactivation and Recovery in Insomnia
Altena, E., van der Werf, Y. D., Sanz‐Arigita, E., Voorn, T., Rombouts, S. A. R. B., Kuijer, J. P. A., & Someren, E. J. W. V. (2008) · SLEEP · doi:10.5665/sleep/31.9.1271 · Cited by 259 · see citing works
Self-citationChronic Insomnia and MRI-Measured Hippocampal Volumes: A Pilot Study
Riemann, D. W., Voderholzer, U., Spiegelhalder, K., Hornyak, M., Buysse, D. J., Nissen, C., Hennig, J., Perlis, M. L., van Elst, L. T., & Feige, B. (2007) · SLEEP · doi:10.1093/sleep/30.8.955 · Cited by 256 · see citing works
Sleep loss affects vigilance: effects of chronic insomnia and sleep therapy
Altena, E., van der Werf, Y. D., STRIJERS, R. L. M., & Someren, E. J. W. V. (2008) · Journal of Sleep Research · doi:10.1111/j.1365-2869.2008.00671.x · Cited by 227 · see citing works
Self-citationWarm pleasant feelings in the brain
Rolls, E. T., Grabenhorst, F., & Parris, B. A. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.03.005 · Cited by 227 · see citing works
Senjem, M. L., Gunter, J. L., Shiung, M. S., Petersen, R. C., & Jack, C. R. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.02.005 · Cited by 206 · see citing works
Chronic Psychophysiological Insomnia: Hyperarousal and/or Inhibition Deficits? An ERPs Investigation
Bastien, C., St-Jean, G., Morin, C. M., Turcotte, I., & Carrier, J. (2008) · SLEEP · doi:10.1093/sleep/31.6.887 · Cited by 132 · see citing works
Raymann, R., & Someren, E. J. W. V. (2008) · SLEEP · doi:10.5665/sleep/31.9.1301 · Cited by 90 · see citing works
Vulnerability of the Orbitofrontal Cortex to Age‐Associated Structural and Functional Brain Changes
Resnick, S. M., Lamar, M., & Driscoll, I. F. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1401.027 · Cited by 74 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Morin, C. M., & Benca, R. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60750-2 · Cited by 976 · see citing works
Connections between sleep and cognition in older adults
Yaffe, K., Falvey, C. M., & Hoang, T. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70172-3 · Cited by 796 · see citing works
Morin, C. M., Drake, C. L., Harvey, A. G., Krystal, A. D., Manber, R., Riemann, D., & Spiegelhalder, K. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.26 · Cited by 746 · see citing works
The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting-state cognition
Diaz, B. A., Van Der Sluis, S., Moens, S., Benjamins, J. S., Migliorati, F., Stoffers, D., Den Braber, A., Poil, S.-S., Hardstone, R., Van't Ent, D., et al. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00446 · Cited by 194 · see citing works
Branger, P., Arenaza-Urquijo, E. M., Tomadesso, C., Mézenge, F., André, C., de Flores, R., Mutlu, J., de La Sayette, V., Eustache, F., Chételat, G., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.009 · Cited by 186 · see citing works
Disrupted Sleep: From Molecules to Cognition
Van Someren, E. J. W., Cirelli, C., Dijk, D.-J., Van Cauter, E., Schwartz, S., & Chee, M. W. L. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2592-15.2015 · Cited by 127 · see citing works
Self-citationSleep, vigilance, and thermosensitivity
Romeijn, N., Raymann, R. J. E. M., Møst, E., Te Lindert, B., Van Der Meijden, W. P., Fronczek, R., Gomez-Herrero, G., & Van Someren, E. J. W. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-1042-2 · Cited by 105 · see citing works
Self-citationStructural brain correlates of human sleep oscillations
Saletin, J. M., van der Helm, E., & Walker, M. P. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.06.021 · Cited by 93 · see citing works
I keep a close watch on this heart of mine: increased interoception in insomnia
Wei, Y., Ramautar, J. R., Colombo, M. A., Stoffers, D., Gómez-Herrero, G., van der Meijden, W. P., te Lindert, B. H. W., van der Werf, Y. D., & Van Someren, E. J. W. (2016) · Sleep · doi:10.5665/sleep.6308 · Cited by 90 · see citing works
Self-citationSleep and dreaming are for important matters
Perogamvros, L., Dang-Vu, T. T., Desseilles, M., & Schwartz, S. (2013) · Frontiers in Psychology · doi:10.3389/fpsyg.2013.00474 · Cited by 77 · see citing works
“In addition, chronic insomnia is characterized by structural abnormalities of reward-related and memory-related structures such as the OFC (Altena et al., 2010), the HC (Riemann et al., 2007), and the ACC (Plante et al., 2012).”
BackgroundInfluentialLloret, M.-A., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D., & Lloret, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031168 · Cited by 68 · see citing works
Self-reported sleep disturbance and incidence of dementia in ageing men
Luojus, M. K., Lehto, S. M., Tolmunen, T., Brem, A.-K., Lönnroos, E., & Kauhanen, J. (2017) · Journal of Epidemiology and Community Health · doi:10.1136/jech-2016-207764 · Cited by 42 · see citing works
Hypnosis in the Management of Sleep Disorders
Becker, P. M. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2014.11.003 · Cited by 37 · see citing works
- Authors
- Altena, E., Vrenken, H., Van Der Werf, Y. D., van den Heuvel, O. A., & Van Someren, E. J. W.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 67
- Issue
- 2
- Pages
- 182-185
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1982924671
- Cited by
- 330
- References
- 20
- Citations by year
- 2026: 19 · 2025: 13 · 2024: 15 · 2023: 20 · 2022: 24 · 2021: 19 · 2020: 31 · 2019: 15 · 2018: 25 · 2017: 27 · 2016: 25 · 2015: 27 · 2014: 17 · 2013: 28 · 2012: 11
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- VU Research Portal (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- chronic insomnia, primary insomnia, orbitofrontal cortex, gray matter volume, precuneus, brain structure, insomnia severity, white matter, decision-making, stimulus processing
- MeSH terms
- Aged, Brain Mapping, Chronic Disease, Female, Humans, Image Processing, Computer-Assisted, Sleep Initiation and Maintenance Disorders, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Fibers, Myelinated, Parietal Lobe, Psychiatric Status Rating Scales, Regression Analysis, Case-Control Studies, Prefrontal Cortex
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
