The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.
Citation: Andrea J. Rapkin, Steven M. Berman, Edythe D. London. The Cerebellum and Premenstrual Dysphoric Disorder[J]. AIMS Neuroscience, 2014, 1(2): 120-141. doi: 10.3934/Neuroscience.2014.2.120
The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.
[1] | Association AP (2013) American Psychiatric Association: Diagnositc and Statistical Manual of Mental Disorders, 5 Eds. American Psychiatric Association: Diagnositc and Statistical Manual of Mental Disorders. |
[2] | Epperson CN (2013) Premenstrual dysphoric disorder and the brain. Am J Psychiatry 170:248-252. doi: 10.1176/appi.ajp.2012.12121555 |
[3] | O'Brien PM, Backstrom T, Brown C, et al. (2011) Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: the ISPMD Montreal consensus. Arch Womens Ment Health 14: 13-21. doi: 10.1007/s00737-010-0201-3 |
[4] | Veith I (1965) The History of a Disease. Chicago: Chicago University Press. |
[5] | Herculano-Houzel S (2010) Coordinated scaling of cortical and cerebellar numbers of neurons. Front Neuroanat 4: 12. |
[6] | Tien RD, Ashdown BC (1992) Crossed cerebellar diaschisis and crossed cerebellar atrophy: correlation of MR findings, clinical symptoms, and supratentorial diseases in 26 patients. AJR Am J Roentgenol 158: 1155-1159. doi: 10.2214/ajr.158.5.1566683 |
[7] | Ito M (1993) New concepts in cerebellar function. Rev Neurol (Paris) 149: 596-599. |
[8] | Harlow HF, Harlow M (1962) Social deprivation in monkeys. Sci Am 207: 136-146. doi: 10.1038/scientificamerican1162-136 |
[9] | Prescott JW (1970) Early somatosensory deprivation as ontogenic process in the abnormal development of the brain and behavior. Medical Primatology 1970: 356-375. |
[10] | Nashold BS, Jr. , Slaughter DG (1969) Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg 31: 172-186. doi: 10.3171/jns.1969.31.2.0172 |
[11] | Heath RG (1977) Modulation of emotion with a brain pacemaker. Treatment for intractable psychiatric illness. J Nerv Ment Dis 165: 300-317. |
[12] | Cooper IS, Amin, L. , Gilman, S. , Waltz, J. M. (1974) The Effect of chronic stimulation of cerebellar cortex on epilepsy in Man. The Cerebellum, Epilepsy and Behavior. New York: Plenum Press. pp. 199-172. |
[13] | Heath RG, Franklin DE, Shraberg D (1979) Gross pathology of the cerebellum in patients diagnosed and treated as functional psychiatric disorders. J Nerv Ment Dis 167: 585-592. doi: 10.1097/00005053-197910000-00001 |
[14] | Heath RG, Llewellyn RC, Rouchell AM (1980) The cerebellar pacemaker for intractable behavioral disorders and epilepsy: follow-up report. Biol Psychiatry 15: 243-256. |
[15] | Heath RG, Franklin DE, Walker CF, et al. (1982) Cerebellar vermal atrophy in psychiatric patients. Biol Psychiatry 17: 569-583. |
[16] | Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121 ( Pt4): 561-579. |
[17] | Schmahmann JD, Weilburg JB, Sherman JC (2007) The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 6: 254-267. doi: 10.1080/14734220701490995 |
[18] | Schmahmann JD (1991) An emerging concept. The cerebellar contribution to higher function. Arch Neurol 48: 1178-1187. |
[19] | Schmahmann JD (1996) From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp 4: 174-198. doi: 10.1002/(SICI)1097-0193(1996)4:3<174::AID-HBM3>3.0.CO;2-0 |
[20] | Allen G, Buxton RB, Wong EC, et al. (1997) Attentional activation of the cerebellum independent of motor involvement. Science 275: 1940-1943. doi: 10.1126/science.275.5308.1940 |
[21] | Stoodley CJ, Schmahmann JD (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 |
[22] | Koziol LF, Budding D, Andreasen N, et al. (2014) Consensus paper: the cerebellum's role in movement and cognition. Cerebellum 13: 151-177. doi: 10.1007/s12311-013-0511-x |
[23] | Schraa-Tam CK, Rietdijk WJ, Verbeke WJ, et al. (2012) fMRI activities in the emotional cerebellum: a preference for negative stimuli and goal-directed behavior. Cerebellum 11: 233-245. doi: 10.1007/s12311-011-0301-2 |
[24] | Ferrucci R, Giannicola G, Rosa M, et al. (2012) Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cogn Emot 26: 786-799. doi: 10.1080/02699931.2011.619520 |
[25] | Grimaldi G, Argyropoulos GP, Boehringer A, et al. (2014) Non-invasive cerebellar stimulation--a consensus paper. Cerebellum 13: 121-138. doi: 10.1007/s12311-013-0514-7 |
[26] | West RL (1996) An application of prefrontal cortex function theory to cognitive aging. Psych Bull120: 272-292. |
[27] | Hogan MJ (2004) The cerebellum in thought and action: a fronto-cerebellar aging hypothesis. New Ideas in Psychology 22: 97-125. doi: 10.1016/j.newideapsych.2004.09.002 |
[28] | Eckert MA (2011) Slowing down: age-related neurobiological predictors of processing speed. Front Neurosci 5: 25. |
[29] | Woodruff-Pak DS, Vogel RW, Ewers M, et al. (2001) MRI-assessed volume of cerebellum correlates with associative learning. Neurobiology of Learning and Memory 76: 342-357. doi: 10.1006/nlme.2001.4026 |
[30] | MacLullich AMJ, Edmond CL, Ferguson KJ, et al. (2004) Size of the neocerebellar vermis is associated with cognition in healthy elderly men. Brain and Cognition 56: 344-348. doi: 10.1016/j.bandc.2004.08.001 |
[31] | Paul R, Grieve SM, Chaudary B, et al. (2009) Relative contributions of the cerebellar vermis and prefrontal lobe volumes on cognitive function across the adult lifespan. Neurobiol Aging 30:457-465. doi: 10.1016/j.neurobiolaging.2007.07.017 |
[32] | Eckert MA, Keren NI, Roberts DR, et al. (2010) Age-related changes in processing speed: unique contributions of cerebellar and prefrontal cortex. Front Hum Neurosci 4: 10. |
[33] | Hogan MJ, Staff RT, Bunting BP, et al. (2011) Cerebellar brain volume accounts for variance in cognitive performance in older adults. Cortex 47: 441-450. doi: 10.1016/j.cortex.2010.01.001 |
[34] | Rasgon N, Serra M, Biggio G, et al. (2001) Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome. Eur J Endocrinol 145: 25-33. doi: 10.1530/eje.0.1450025 |
[35] | Hamakawa H, Kato T, Murashita J, et al. (1998) Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Eur Arch Psychiatry Clin Neurosci 248: 53-58. doi: 10.1007/s004060050017 |
[36] | Renshaw PF, Levin JM, Kaufman MJ, et al. (1997) Dynamic susceptibility contrast magnetic resonance imaging in neuropsychiatry: present utility and future promise. Eur Radiol 7 Suppl 5:216-221. |
[37] | Buchpiguel C, Alavi A, Crawford D, et al. (2000) Changes in cerebral blood flow associated with premenstrual syndrome: a preliminary study. J Psychosom Obstet Gynaecol 21: 157-165. doi: 10.3109/01674820009075623 |
[38] | Rasgon NL, Thomas MA, Guze BH, et al. (2001) Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study. Psychiatry Res 106: 47-57. doi: 10.1016/S0925-4927(00)00085-8 |
[39] | Epperson CN, Haga K, Mason GF, et al. (2002) Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 59: 851-858. doi: 10.1001/archpsyc.59.9.851 |
[40] | Jovanovic H, Cerin A, Karlsson P, et al. (2006) A PET study of 5-HT1A receptors at different phases of the menstrual cycle in women with premenstrual dysphoria. Psychiatry Res 148:185-193. doi: 10.1016/j.pscychresns.2006.05.002 |
[41] | Eriksson O, Wall A, Marteinsdottir I, et al. (2006) Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria. Psychiatry Res 146: 107-116. doi: 10.1016/j.pscychresns.2005.02.012 |
[42] | Batra NA, Seres-Mailo J, Hanstock C, et al. (2008) Proton magnetic resonance spectroscopy measurement of brain glutamate levels in premenstrual dysphoric disorder. Biol Psychiatry 63:1178-1184. doi: 10.1016/j.biopsych.2007.10.007 |
[43] | Protopopescu X, Tuescher O, Pan H, et al. (2008) Toward a functional neuroanatomy of premenstrual dysphoric disorder. J Affect Disord 108: 87-94. doi: 10.1016/j.jad.2007.09.015 |
[44] | Bannbers E, Gingnell M, Engman J, et al. (2012) The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition. J Affect Disord 142:347-350. doi: 10.1016/j.jad.2012.04.006 |
[45] | Gingnell M, Morell A, Bannbers E, et al. (2012) Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder. Horm Behav 62: 400-406. doi: 10.1016/j.yhbeh.2012.07.005 |
[46] | Gingnell M, Bannbers E, Wikstrom J, et al. (2013) Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli. Eur Neuropsychopharmacol 23: 1474-1483. doi: 10.1016/j.euroneuro.2013.08.002 |
[47] | Baller EB, Wei SM, Kohn PD, et al. (2013) Abnormalities of dorsolateral prefrontal function in women with premenstrual dysphoric disorder: a multimodal neuroimaging study. Am J Psychiatry170: 305-314. |
[48] | Jeong HG, Ham BJ, Yeo HB, et al. (2012) Gray matter abnormalities in patients with premenstrual dysphoric disorder: an optimized voxel-based morphometry. J Affect Disord 140: 260-267. doi: 10.1016/j.jad.2012.02.010 |
[49] | Berman SM, London ED, Morgan M, et al. (2013) Elevated gray matter volume of the emotional cerebellum in women with premenstrual dysphoric disorder. J Affect Disord 146: 266-271. doi: 10.1016/j.jad.2012.06.038 |
[50] | Rapkin A (2003) A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder. Psychoneuroendocrinology 28 Suppl 3: 39-53. |
[51] | Halbreich U (2008) Selective serotonin reuptake inhibitors and initial oral contraceptives for the treatment of PMDD: effective but not enough. CNS Spectr 13: 566-572. doi: 10.1017/S1092852900016849 |
[52] | Nevatte T, O'Brien PM, Backstrom T, et al. (2013) ISPMD consensus on the management of premenstrual disorders. Arch Womens Ment Health 16: 279-291. doi: 10.1007/s00737-013-0346-y |
[53] | Raichle M (1987) Circulatory and Metabolic Correlates of brain function in normal humans. Handbook of Physiology-The nervous system Bethesda: American Physiological Society V:643-674. |
[54] | Rapkin AJ, Berman SM, Mandelkern MA, et al. (2011) Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biol Psychiatry 69: 374-380. doi: 10.1016/j.biopsych.2010.09.029 |
[55] | Mackenzie G, Maguire J (2014) The role of ovarian hormone-derived neurosteroids on the regulation of GABA receptors in affective disorders. Psychopharmacology (Berl). |
[56] | Schmidt PJ, Nieman LK, Danaceau MA, et al. (1998) Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. New England Journal of Medicine 338: 209-216. doi: 10.1056/NEJM199801223380401 |
[57] | Hanstock C, Allen, PS (2000) Segmentation of brain from a PRESS localized single volume using double inversion recovery for simultaneous T1 nulling. 8th Annual Meeting of the International Society for Magnetic Resonance in Medicine. Denver, Colorado. |
[58] | Diedrichsen J, Balsters JH, Flavell J, et al. (2009) A probabilistic MR atlas of the human cerebellum. Neuroimage 46: 39-46. doi: 10.1016/j.neuroimage.2009.01.045 |
[59] | Kalpouzos G, Persson J, Nyberg L (2012) Local brain atrophy accounts for functional activity differences in normal aging. Neurobiol Aging 33: 623 e621-623 e613. |
[60] | Diedrichsen J, Verstynen T, Schlerf J, et al. (2010) Advances in functional imaging of the human cerebellum. Curr Opin Neurol 23: 382-387. |
[61] | Baldacara L, Nery-Fernandes F, Rocha M, et al. (2011) Is cerebellar volume related to bipolar disorder? J Affect Disord 135: 305-309. doi: 10.1016/j.jad.2011.06.059 |
[62] | De Bellis MD, Kuchibhatla M (2006) Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 60: 697-703. doi: 10.1016/j.biopsych.2006.04.035 |
[63] | Frodl TS, Koutsouleris N, Bottlender R, et al. (2008) Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry 65: 1156-1165. doi: 10.1001/archpsyc.65.10.1156 |
[64] | Peng J, Liu J, Nie B, et al. (2011) Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study. Eur J Radiol 80:395-399. doi: 10.1016/j.ejrad.2010.04.006 |
[65] | Kim D, Cho HB, Dager SR, et al. (2013) Posterior cerebellar vermal deficits in bipolar disorder. J Affect Disord 150: 499-506. doi: 10.1016/j.jad.2013.04.050 |
[66] | Schutter DJ, Koolschijn PC, Peper JS, et al. (2012) The cerebellum link to neuroticism: a volumetric MRI association study in healthy volunteers. PLoS One 7: e37252. doi: 10.1371/journal.pone.0037252 |
[67] | Adler CM, DelBello MP, Jarvis K, et al. (2007) Voxel-based study of structural changes in first-episode patients with bipolar disorder. Biol Psychiatry 61: 776-781. doi: 10.1016/j.biopsych.2006.05.042 |
[68] | Spinelli S, Chefer S, Suomi SJ, et al. (2009) Early-life stress induces long-term morphologic changes in primate brain. Arch Gen Psychiatry 66: 658-665. doi: 10.1001/archgenpsychiatry.2009.52 |
[69] | Draganski B, Gaser C, Busch V, et al. (2004) Neuroplasticity: changes in grey matter induced by training. Nature 427: 311-312. doi: 10.1038/427311a |
[70] | Kwok V, Niu Z, Kay P, et al. (2011) Learning new color names produces rapid increase in gray matter in the intact adult human cortex. Proc Natl Acad Sci U S A 108: 6686-6688. doi: 10.1073/pnas.1103217108 |
[71] | Oral E, Ozcan H, Kirkan TS, et al. (2013) Luteal serum BDNF and HSP70 levels in women with premenstrual dysphoric disorder. Eur Arch Psychiatry Clin Neurosci 263: 685-693. doi: 10.1007/s00406-013-0398-z |
[72] | Anim-Nyame N, Domoney C, Panay N, et al. (2000) Plasma leptin concentrations are increased in women with premenstrual syndrome. Hum Reprod 15: 2329-2332. doi: 10.1093/humrep/15.11.2329 |
[73] | Oldreive CE, Harvey J, Doherty GH (2008) Neurotrophic effects of leptin on cerebellar Purkinje but not granule neurons in vitro. Neurosci Lett 438: 17-21. doi: 10.1016/j.neulet.2008.04.045 |
[74] | Riad-Gabriel MG, Jinagouda SD, Sharma A, et al. (1998) Changes in plasma leptin during the menstrual cycle. Eur J Endocrinol 139: 528-531. doi: 10.1530/eje.0.1390528 |
[75] | Narita K, Kosaka H, Okazawa H, et al. (2009) Relationship between plasma leptin level and brain structure in elderly: a voxel-based morphometric study. Biol Psychiatry 65: 992-994. doi: 10.1016/j.biopsych.2008.10.006 |
[76] | Matochik JA, London ED, Yildiz BO, et al. (2005) Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J Clin Endocrinol Metab 90: 2851-2854. doi: 10.1210/jc.2004-1979 |
[77] | London ED, Berman SM, Chakrapani S, et al. (2011) Short-term plasticity of gray matter associated with leptin deficiency and replacement. J Clin Endocrinol Metab 96: E1212-1220. doi: 10.1210/jc.2011-0314 |
[78] | Tommaselli GA, Di Carlo C, Bifulco G, et al. (2003) Serum leptin levels in patients with premenstrual syndrome treated with GnRH analogues alone and in association with tibolone. Clin Endocrinol (Oxf) 59: 716-722. doi: 10.1046/j.1365-2265.2003.01911.x |
[79] | Akturk M, Toruner F, Aslan S, et al. (2013) Circulating insulin and leptin in women with and without premenstrual disphoric disorder in the menstrual cycle. Gynecol Endocrinol 29: 465-469. doi: 10.3109/09513590.2013.769512 |
[80] | Eikelis N, Esler M, Barton D, et al. (2006) Reduced brain leptin in patients with major depressive disorder and in suicide victims. Mol Psychiatry 11: 800-801. doi: 10.1038/sj.mp.4001862 |
[81] | Westling S, Ahren B, Traskman-Bendz L, et al. (2004) Low CSF leptin in female suicide attempters with major depression. J Affect Disord 81: 41-48. doi: 10.1016/j.jad.2003.07.002 |
[82] | Yoshida-Komiya H, Takano K, Fujimori K, et al. (2014) Plasma levels of leptin in reproductive-aged women with mild depressive and anxious states. Psychiatry Clin Neurosci. |
[83] | Lawson EA, Miller KK, Blum JI, et al. (2012) Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat. Clin Endocrinol (Oxf) 76: 520-525. doi: 10.1111/j.1365-2265.2011.04182.x |
[84] | Chirinos DA, Goldberg R, Gellman M, et al. (2013) Leptin and its association with somatic depressive symptoms in patients with the metabolic syndrome. Ann Behav Med 46: 31-39. doi: 10.1007/s12160-013-9479-5 |
[85] | Kloiber S, Ripke S, Kohli MA, et al. (2013) Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels. Eur Neuropsychopharmacol 23: 653-662. doi: 10.1016/j.euroneuro.2012.08.010 |
[86] | Johnston JM, Greco SJ, Hamzelou A, et al. (2011) Repositioning leptin as a therapy for Alzheimer's disease. Therapy 8: 481-490. doi: 10.2217/thy.11.57 |
[87] | Johnston J HW, Fardo D, Greco S, Perry G, Montine T, Trojanowski J, Shaw L, Ashford J, Tezapsidis N (2013) For The Alzheimer's Disease Neuroimaging Initiative. Low Plasma Leptin in Cognitively Impaired ADNI Subjects- Gender Differences and Diagnostic and Therapeutic Potential. Curr Alzheimer Res. |
[88] | Rapkin AJ, Morgan M, Goldman L, et al. (1997) Progesterone metabolite allopregnanolone in women with premenstrual syndrome. Obstet Gynecol 90: 709-714. doi: 10.1016/S0029-7844(97)00417-1 |
[89] | Singh M, Su C (2013) Progesterone and neuroprotection. Horm Behav 63: 284-290. doi: 10.1016/j.yhbeh.2012.06.003 |
[90] | Azcoitia I, Arevalo MA, De Nicola AF, et al. (2011) Neuroprotective actions of estradiol revisited. Trends Endocrinol Metab 22: 467-473. doi: 10.1016/j.tem.2011.08.002 |
[91] | Gao Q, Horvath TL (2008) Cross-talk between estrogen and leptin signaling in the hypothalamus. Am J Physiol Endocrinol Metab 294: E817-826. doi: 10.1152/ajpendo.00733.2007 |
[92] | Hedges VL, Ebner TJ, Meisel RL, et al. (2012) The cerebellum as a target for estrogen action. Front Neuroendocrinol 33: 403-411. doi: 10.1016/j.yfrne.2012.08.005 |
[93] | Ghidoni R, Boccardi M, Benussi L, et al. (2006) Effects of estrogens on cognition and brain morphology: involvement of the cerebellum. Maturitas 54: 222-228. doi: 10.1016/j.maturitas.2005.11.002 |
[94] | Boccardi M, Ghidoni R, Govoni S, et al. (2006) Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study. Menopause 13: 584-591. doi: 10.1097/01.gme.0000196811.88505.10 |
[95] | Robertson D, Craig M, van Amelsvoort T, et al. (2009) Effects of estrogen therapy on age-related differences in gray matter concentration. Climacteric 12: 301-309. doi: 10.1080/13697130902730742 |
[96] | Kim SG, Ogawa S (2012) Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab 32: 1188-1206. doi: 10.1038/jcbfm.2012.23 |
[97] | D'Esposito M, Deouell LY, Gazzaley A. (2003) Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci 4: 863-872. doi: 10.1038/nrn1246 |
[98] | Ances BM, Liang CL, Leontiev O, et al. (2009) Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation. Hum Brain Mapp 30: 1120-1132. doi: 10.1002/hbm.20574 |
[99] | Gauthier CJ, Madjar C, Desjardins-Crepeau L, et al. (2013) Age dependence of hemodynamic response characteristics in human functional magnetic resonance imaging. Neurobiol Aging 34:1469-1485. doi: 10.1016/j.neurobiolaging.2012.11.002 |
[100] | Sui R, Zhang L (2012) Cerebellar dysfunction may play an important role in vascular dementia. Med Hypotheses 78: 162-165. doi: 10.1016/j.mehy.2011.10.017 |
[101] | arrett DD, Kovacevic N, McIntosh AR, et al. (2010) Blood oxygen level-dependent signal variability si more than just noise. J Neurosci 30: 4914-4921. |
[102] | Grady CL, Garrett DD (2013) Understanding variability in the BOLD signal and why it matters for aging. Brain Imaging Behav. |