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Neurotherapeutics logoLink to Neurotherapeutics
. 2007 Jul;4(3):360–370. doi: 10.1016/j.nurt.2007.05.007

Advances in functional magnetic resonance imaging: Technology and clinical applications

Bradford C Dickerson 1,2,3,4,
PMCID: PMC7479713  PMID: 17599702

Summary

Functional MRI (fMRI) is a valuable method for use by clinical investigators to study task-related brain activation in patients with neurological or neuropsychiatric illness. Despite the relative infancy of the field, the rapid adoption of this functional neuroimaging technology has resulted from, among other factors, its ready availability, its relatively high spatial and temporal resolution, and its safety as a noninvasive imaging tool that enables multiple repeated scans over the course of a longitudinal study, and thus may lend itself well as a measure in clinical drug trials. Investigators have used fMRI to identify abnormal functional brain activity during task performance in a variety of patient populations, including those with neurodegenerative, demyelinating, cerebrovascular, and other neurological disorders that highlight the potential utility of fMRI in both basic and clinical spheres of research. In addition, fMRI studies reveal processes related to neuroplasticity, including compensatory hyperactivation, which may be a universally-occurring, adaptive neural response to insult. Functional MRI is being used to study the modulatory effects of genetic risk factors for neurological disease on brain activation; it is being applied to differential diagnosis, as a predictive biomarker of disease course, and as a means to identify neural correlates of neurotherapeutic interventions. Technological advances are rapidly occurring that should provide new applications for fMRI, including improved spatial resolution, which promises to reveal novel insights into the function of fine-scale neural circuitry of the human brain in health and disease.

Key Words: Alzheimer’s disease, mild cognitive impairment, plasticity, functional magnetic resonance imaging

References

  • 1.Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ. Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry. Cereb Cortex. 2007;17:951–961. doi: 10.1093/cercor/bhl006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Holt DJ, Kunkel L, Weiss AP, et al. Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia. Schizophr Res. 2006;82:153–162. doi: 10.1016/j.schres.2005.09.021. [DOI] [PubMed] [Google Scholar]
  • 3.Thermenos HW, Scidman LJ, Poldrack RA, et al. Elaborative verbal encoding and altered anterior parahippocampal activation in adolescents and young adults at genetic risk for schizophrenia using FMRI. Biol Psychiatry. 2007;61:564–574. doi: 10.1016/j.biopsych.2006.04.044. [DOI] [PubMed] [Google Scholar]
  • 4.Dickerson BC, Sperling RA. Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer’s disease. Neurorx. 2005;2:348–360. doi: 10.1602/neurorx.2.2.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Burock MA, Buckner RL, Woldorff MG, Rosen BR, Dale AM. Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI. Neuroreport. 1998;9:3735–3739. doi: 10.1097/00001756-199811160-00030. [DOI] [PubMed] [Google Scholar]
  • 6.Rice CJ, Fristen KJ. Scanning patients with tasks they can perform. Hum Brain Mapp. 1999;8:102–108. doi: 10.1002/(SICI)1097-0193(1999)8:2/3<102::AID-HBM6>3.0.CO;2-J. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Machielsen WC, Rombouts SA, Barkhof F, Scheltens P, Witter MP. FMRI of visual encoding: reproducibility of activation. Hum Brain Mapp. 2000;9:156–164. doi: 10.1002/(SICI)1097-0193(200003)9:3<156::AID-HBM4>3.0.CO;2-Q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Manoach DS, Halpern EF, Kramer TS, et al. Test-retest reliability of a functional MRI working memory paradigm in normal and schizophrenic subjects. Am J Psychiatry. 2001;158:955–958. doi: 10.1176/appi.ajp.158.6.955. [DOI] [PubMed] [Google Scholar]
  • 9.Sperling R, Greve D, Dale A, et al. Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A. 2002;99:455–460. doi: 10.1073/pnas.012467899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–1384. doi: 10.1016/j.neurobiolaging.2005.09.012. [DOI] [PubMed] [Google Scholar]
  • 11.Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science. 2002;298:789–791. doi: 10.1126/science.1074069. [DOI] [PubMed] [Google Scholar]
  • 12.Coleman P, Federoff H, Kurlan R. A focus on the synapse for neuroprotection in Alzheimer disease and other dementias. Neurology. 2004;63:1155–1162. doi: 10.1212/01.wnl.0000140626.48118.0a. [DOI] [PubMed] [Google Scholar]
  • 13.Buckner RL, Snyder AZ, Sanders AL, Raichle ME, Morris JC. Functional brain imaging of young, nondemented, and demented older adults. J Cogn Neurosci. 2000;12(suppl 2):24–34. doi: 10.1162/089892900564046. [DOI] [PubMed] [Google Scholar]
  • 14.D’Esposito M, Deouell LY, Gazzaley A. Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci. 2003;4:863–872. doi: 10.1038/nrn1246. [DOI] [PubMed] [Google Scholar]
  • 15.Grossman M, Koenig P, DeVita C, et al. Neural basis for verb processing in Alzheimer’s disease: an fMRI study. Neuropsychology. 2003;17:658–674. doi: 10.1037/0894-4105.17.4.658. [DOI] [PubMed] [Google Scholar]
  • 16.Johnson SC, Saykin AJ, Baxter LC, et al. The relationship between fMRI activation and cerebral atrophy: comparison of normal aging and Alzheimer disease. Neuroimage. 2000;11:179–187. doi: 10.1006/nimg.1999.0530. [DOI] [PubMed] [Google Scholar]
  • 17.Saykin AJ, Flashman LA, Frutiger SA, et al. Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: patterns of functional MRI activation. J Int Neuropsychol Soc. 1999;5:377–392. doi: 10.1017/s135561779955501x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Grossman M, Koenig P, Glosser G, et al. Neural basis for semantic memory difficulty in Alzheimer’s disease: an fMRI study. Brain. 2003;126:292–311. doi: 10.1093/brain/awg027. [DOI] [PubMed] [Google Scholar]
  • 19.Thulbom KR, Martin C, Voyvodic JT. Functional MR imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer’s disease and in cognitively able elderly volunteers. AJNR Am J Neuroradiol. 2000;21:524–531. [PMC free article] [PubMed] [Google Scholar]
  • 20.Small SA, Perera GM, DeLaPaz R, Mayeux R, Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease. Ann Neurol. 1999;45:466–472. doi: 10.1002/1531-8249(199904)45:4<466::aid-ana8>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  • 21.Rombouts SA, Barkhof F, Veltman DJ, et al. Functional MR imaging in Alzheimer’s disease during memory encoding. AJNR Am J Neuroradiol. 2000;21:1869–1875. [PMC free article] [PubMed] [Google Scholar]
  • 22.Kato T, Knopman D, Liu H. Dissociation of regional activation in mild AD during visual encoding: a functional MRI study. Neurology. 2001;57:812–816. doi: 10.1212/wnl.57.5.812. [DOI] [PubMed] [Google Scholar]
  • 23.Sperling RA, Bates JF, Chua EF, et al. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003;74:44–50. doi: 10.1136/jnnp.74.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Machulda MM, Ward HA, Borowski B, et al. Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients. Neurology. 2003;61:500–506. doi: 10.1212/01.wnl.0000079052.01016.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Celone KA, Calhoun VD, Dickerson BC, et al. Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci. 2006;26:10222–10231. doi: 10.1523/JNEUROSCI.2250-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Rombouts SARB, Goekoop R, Stam CJ, Barkhof F, Scheltens P. Delayed rather than decreased BOLD response as a marker for early Alzheimer’s disease. Neuroimage. 2005;26:1078–1085. doi: 10.1016/j.neuroimage.2005.03.022. [DOI] [PubMed] [Google Scholar]
  • 27.Dickerson BC, Salat DH, Bates JF, et al. Medial temporal lobe function and structure in mild cognitive impairment. Ann Neurol. 2004;56:27–35. doi: 10.1002/ana.20163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Dickerson BC, Salat DH, Greve DN, et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology. 2005;65:404–411. doi: 10.1212/01.wnl.0000171450.97464.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Hamalainen A, Pihlajamaki M, Tanila H, et al. Increased fMRI responses during encoding in mild cognitive impairment. Neurobiol Aging September 22, 2006 [Epub ahead of print]. [DOI] [PubMed]
  • 30.Sperling R, Chua E, Cocchiarella A, et al. Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation. Neuroimage. 2003;20:1400–1410. doi: 10.1016/S1053-8119(03)00391-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Kircher T, Weis S, Freymann K, et al. Hippocampal activation in MCI patients is necessary for successful memory encoding. J Neurol Neurosurg Psychiatry February 7, 2007 [Epub ahead of print]. [DOI] [PMC free article] [PubMed]
  • 32.Rosas HD, Feigin AS, Hersch SM. Using advances in neuroimaging to detect, understand, and monitor disease progression in Huntington’s disease. NeuroRx. 2004;1:263–272. doi: 10.1602/neurorx.1.2.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Monchi O, Petrides M, Doyon J, Postuma RB, Worsley K, Dagher A. Neural bases of set-shifting deficits in Parkinson’s disease. J Neurosci. 2004;24:702–710. doi: 10.1523/JNEUROSCI.4860-03.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Johansen-Berg H, Dawes H, Guy C, Smith SM, Wade DT, Matthews PM. Correlation between motor improvements and altered fMRI activity after rehabilitative therapy. Brain. 2002;125:2731–2742. doi: 10.1093/brain/awf282. [DOI] [PubMed] [Google Scholar]
  • 35.Carey JR, Kimberley TJ, Lewis SM, et al. Analysis of fMRI and finger tracking training in subjects with chronic stroke. Brain. 2002;125:773–788. doi: 10.1093/brain/awf091. [DOI] [PubMed] [Google Scholar]
  • 36.Reddy H, Narayanan S, Amoutelis R, et al. Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain. 2000;123:2314–2320. doi: 10.1093/brain/123.11.2314. [DOI] [PubMed] [Google Scholar]
  • 37.Morgen K, Kadom N, Sawaki L, et al. Training-dependent plasticity in patients with multiple sclerosis. Brain. 2004;127:2506–2517. doi: 10.1093/brain/awh266. [DOI] [PubMed] [Google Scholar]
  • 38.Buckle GJ. Functional magnetic resonance imaging and multiple sclerosis: the evidence for neuronal plasticity. J Neuroimaging. 2005;15:82S–93S. doi: 10.1177/1051228405284093. [DOI] [PubMed] [Google Scholar]
  • 39.McAllister TW, Saykin AJ, Flashman LA, et al. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology. 1999;53:1300–1308. doi: 10.1212/wnl.53.6.1300. [DOI] [PubMed] [Google Scholar]
  • 40.Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology. 2002;59:1343–1349. doi: 10.1212/01.wnl.0000031811.45569.b0. [DOI] [PubMed] [Google Scholar]
  • 41.Desmond JE, Chen SH, DeRosa E, Pryor MR, Pfefferbaum A, Sullivan EV. Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study. Neuroimage. 2003;19:1510–1520. doi: 10.1016/s1053-8119(03)00102-2. [DOI] [PubMed] [Google Scholar]
  • 42.Callicott JH, Mattay VS, Verchinski BA, Marenco S, Egan MF, Weinberger DR. Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am J Psychiatry. 2003;160:2209–2215. doi: 10.1176/appi.ajp.160.12.2209. [DOI] [PubMed] [Google Scholar]
  • 43.Drummond SP, Brown GG, Gillin JC, Stricker JL, Wong EC, Buxton RB. Altered brain response to verbal learning following sleep deprivation. Nature. 2000;403:655–657. doi: 10.1038/35001068. [DOI] [PubMed] [Google Scholar]
  • 44.Cabeza R, Anderson ND, Locantore JK, McIntosh AR. Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage. 2002;17:1394–1402. doi: 10.1006/nimg.2002.1280. [DOI] [PubMed] [Google Scholar]
  • 45.Winterer G, Hariri AR, Goldman D, Weinberger DR. Neuroimaging and human genetics. Int Rev Neurobiol. 2005;67:325–383. doi: 10.1016/S0074-7742(05)67010-9. [DOI] [PubMed] [Google Scholar]
  • 46.Hariri AR, Weinberger DR. Functional neuroimaging of genetic variation in serotonergic neurotransmission. Genes Brain Behav. 2003;2:341–349. doi: 10.1046/j.1601-1848.2003.00048.x. [DOI] [PubMed] [Google Scholar]
  • 47.Saunders AM. Apolipoprotein E and Alzheimer disease: an update on genetic and functional analyses. J Neuropathol Exp Neurol. 2000;59:751–758. doi: 10.1093/jnen/59.9.751. [DOI] [PubMed] [Google Scholar]
  • 48.Smith CD, Andersen AH, Kryscio RJ, et al. Altered brain activation in cognitively intact individuals at high risk for Alzheimer’s disease. Neurology. 1999;53:1391–1396. doi: 10.1212/wnl.53.7.1391. [DOI] [PubMed] [Google Scholar]
  • 49.Smith CD, Andersen AH, Kryscio RJ, et al. Women at risk for AD show increased parietal activation during a fluency task. Neurology. 2002;58:1197–1202. doi: 10.1212/wnl.58.8.1197. [DOI] [PubMed] [Google Scholar]
  • 50.Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med. 2000;343:450–456. doi: 10.1056/NEJM200008173430701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Bondi MW, Houston WS, Eyler LT, Brown GG. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease. Neurology. 2005;64:501–508. doi: 10.1212/01.WNL.0000150885.00929.7E. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Johnson SC, Schmitz TW, Trivedi MA, et al. The influence of Alzheimer disease family history and apolipoprotein E e4 on mesial temporal lobe activation. J Neurosci. 2006;26:6069–6076. doi: 10.1523/JNEUROSCI.0959-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Gron G, Bittner D, Schmitz B, Wunderlich AP, Riepe MW. Subjective memory complaints: objective neural markers in patients with Alzheimer’s disease and major depressive disorder. Ann Neurol. 2002;51:491–498. doi: 10.1002/ana.10157. [DOI] [PubMed] [Google Scholar]
  • 54.Rombouts SA, van Swieten JC, Pijnenburg YA, Goekoop R, Barkhof F, Scheltens P. Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD. Neurology. 2003;60:1904–1908. doi: 10.1212/01.wnl.0000069462.11741.ec. [DOI] [PubMed] [Google Scholar]
  • 55.Miller S, Bates J, Blacker D, Sperling RA, Dickerson BC. Hippocampal activation in MCI predicts subsequent cognitive decline. Presented at the International Conference on Alzheimer’s Disease; July 17, 2006; Madrid.
  • 56.Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Roc Natl Acad Sci U S A. 2001;98:676–682. doi: 10.1073/pnas.98.2.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Lustig C, Snyder AZ, Bhakta M, et al. Functional deactivations: change with age and dementia of the Alzheimer type. Proc Natl Acad Sci U S A. 2003;100:14504–14509. doi: 10.1073/pnas.2235925100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004;101:4637–4642. doi: 10.1073/pnas.0308627101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Rombouts SARB, Barkhof F, Goekoop R, Stam CJ, Scheltens P. Altered resting state networks in mild cognitive impairment and mild Alzheimer’s disease: an fMRI study. Hum Brain Mapp. 2005;26:231–239. doi: 10.1002/hbm.20160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25:7709–7717. doi: 10.1523/JNEUROSCI.2177-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Ward NS, Frackowiak RS. The functional anatomy of cerebral reorganization after focal brain injury. J Physiol Paris. 2006;99:425–436. doi: 10.1016/j.jphysparis.2006.03.002. [DOI] [PubMed] [Google Scholar]
  • 62.Hodics T, Cohen LG, Cramer SC. Functional imaging of intervention effects in stroke motor rehabilitation. Arch Phys Med Rehabil. 2006;87:S36–S42. doi: 10.1016/j.apmr.2006.09.005. [DOI] [PubMed] [Google Scholar]
  • 63.Stinear CM, Barber PA, Smale PR, Coxon JP, Fleming MK, Byblow WD. Functional potential in chronic stroke patients depends on corticospinal tract integrity. Brain. 2007;130:170–180. doi: 10.1093/brain/awl333. [DOI] [PubMed] [Google Scholar]
  • 64.McGonigle DJ, Hanninen R, Salenius S, Hari R, Frackowiak RS, Frith CD. Whose arm is it anyway? An fMRI case study of supernumerary phantom limb. Brain. 2002;125:1265–1274. doi: 10.1093/brain/awf139. [DOI] [PubMed] [Google Scholar]
  • 65.Maguire EA, Vargha-Khadem F, Mishkin M. The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval. Brain. 2001;124:1156–1170. doi: 10.1093/brain/124.6.1156. [DOI] [PubMed] [Google Scholar]
  • 66.Moo LR, Slotnick SD, Krauss G, Hart J. A prospective study of motor recovery following multiple subpial transections. Neuroreport. 2002;13:665–669. doi: 10.1097/00001756-200204160-00026. [DOI] [PubMed] [Google Scholar]
  • 67.Mondadori CR, Buchmann A, Mustovic H, et al. Enhanced brain activity may precede the diagnosis of Alzheimer’s disease by 30 years. Brain. 2006;129:2908–2922. doi: 10.1093/brain/awl266. [DOI] [PubMed] [Google Scholar]
  • 68.Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006;313:1402–1402. doi: 10.1126/science.1130197. [DOI] [PubMed] [Google Scholar]
  • 69.Leslie RA, James MF. Pharmacological magnetic resonance imaging: a new application for functional MRI. Trends Pharmacol Sci. 2000;21:314–318. doi: 10.1016/s0165-6147(00)01507-8. [DOI] [PubMed] [Google Scholar]
  • 70.Honey G, Bullmore E. Human pharmacological MRI. Trends Pharmacol Sci. 2004;25:366–374. doi: 10.1016/j.tips.2004.05.009. [DOI] [PubMed] [Google Scholar]
  • 71.Mattay VS, Callicott JH, Bertolino A, et al. Effects of dextroamphetamine on cognitive performance and cortical activation. Neuroimage. 2000;12:268–275. doi: 10.1006/nimg.2000.0610. [DOI] [PubMed] [Google Scholar]
  • 72.Thiel CM, Henson RN, Morris JS, Fristen KJ, Dolan RJ. Pharmacological modulation of behavioral and neuronal correlates of repetition priming. J Neurosci. 2001;21:6846–6852. doi: 10.1523/JNEUROSCI.21-17-06846.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Coull JT, Nobre AC, Frith CD. The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting. Cereb Cortex. 2001;11:73–84. doi: 10.1093/cercor/11.1.73. [DOI] [PubMed] [Google Scholar]
  • 74.Goldstein JM, Jerram M, Poldrack R, et al. Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging. J Neurosci. 2005;25:9309–9316. doi: 10.1523/JNEUROSCI.2239-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Goekoop R, Barkhof F, Duschek EJ, et al. Raloxifene treatment enhances brain activation during recognition of familiar items: a pharmacological fMRI study in healthy elderly males. Neuropsychopharmacology. 2006;31:1508–1518. doi: 10.1038/sj.npp.1300956. [DOI] [PubMed] [Google Scholar]
  • 76.Gibbs SE, D’Esposito M. Individual capacity differences predict working memory performance and prefrontal activity following dopamine receptor stimulation. Cogn Affect Behav Neurosci. 2005;5:212–221. doi: 10.3758/cabn.5.2.212. [DOI] [PubMed] [Google Scholar]
  • 77.Breiter HC, Gollub RL, Weisskoff RM, et al. Acute effects of cocaine on human brain activity and emotion. Neuron. 1997;19:591–611. doi: 10.1016/s0896-6273(00)80374-8. [DOI] [PubMed] [Google Scholar]
  • 78.Kalin NH, Davidson RJ, Irwin W, et al. Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine. J Clin Psychiatry. 1997;58(suppl 16):32–39. [PubMed] [Google Scholar]
  • 79.Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, Sharma T. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci USA. 1999;96:13432–13437. doi: 10.1073/pnas.96.23.13432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Mattay VS, Tessitore A, Callicott JH, et al. Dopaminergic modulation of cortical function in patients with Parkinson’s disease. Ann Neurol. 2002;51:156–164. doi: 10.1002/ana.10078. [DOI] [PubMed] [Google Scholar]
  • 81.Fu CH, Williams SC, Cleare AJ, et al. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry. 2004;61:877–889. doi: 10.1001/archpsyc.61.9.877. [DOI] [PubMed] [Google Scholar]
  • 82.Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003;160:64–75. doi: 10.1176/appi.ajp.160.1.64. [DOI] [PubMed] [Google Scholar]
  • 83.Bertolino A, Caforio G, Blasi G, et al. Interaction of COMT (Val[108/158]Met) genotype and olanzapine treatment on pre-frontal cortical function in patients with schizophrenia. Am J Psychiatry. 2004;161:1798–1805. doi: 10.1176/ajp.161.10.1798. [DOI] [PubMed] [Google Scholar]
  • 84.Schon K, Atri A, Hasselmo ME, Tricarico MD, LoPresti ML, Stem CE. Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans. J Neurosci. 2005;25:9112–9123. doi: 10.1523/JNEUROSCI.1982-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Thiel CM, Henson RN, Dolan RJ. Scopolamine but not lorazepam modulates face repetition priming: a psychopharmacological fMRI study. Neuropsychopharmacology. 2002;27:282–292. doi: 10.1016/S0893-133X(02)00316-0. [DOI] [PubMed] [Google Scholar]
  • 86.Thiel CM, Bentley P, Dolan RJ. Effects of cholinergic enhancement on conditioning-related responses in human auditory cortex. Eur J Neurosci. 2002;16:2199–2206. doi: 10.1046/j.1460-9568.2002.02272.x. [DOI] [PubMed] [Google Scholar]
  • 87.Thiel CM, Fristen KJ, Dolan RJ. Cholinergic modulation of experience-dependent plasticity in human auditory cortex. Neuron. 2002;35:567–574. doi: 10.1016/s0896-6273(02)00801-2. [DOI] [PubMed] [Google Scholar]
  • 88.Bentley P, Vuilleumier P, Thiel CM, Driver J, Dolan RJ. Effects of attention and emotion on repetition priming and their modulation by cholinergic enhancement. J Neurophysiol. 2003;90:1171–1181. doi: 10.1152/jn.00776.2002. [DOI] [PubMed] [Google Scholar]
  • 89.Wink AM, Bernard F, Salvador R, Bullmore E, Suckling J. Age and cholinergic effects on hemodynamics and functional coherence of human hippocampus. Neurobiol Aging. 2006;27:1395–1404. doi: 10.1016/j.neurobiolaging.2005.08.011. [DOI] [PubMed] [Google Scholar]
  • 90.Rombouts SA, Barkhof F, Van Meel CS, Scheltens P. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2002;73:665–671. doi: 10.1136/jnnp.73.6.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Saykin AJ, Wishart HA, Rabin LA, et al. Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain. 2004;127:1574–1583. doi: 10.1093/brain/awh177. [DOI] [PubMed] [Google Scholar]
  • 92.Goekoop R, Rombouts SA, Jonker C, et al. Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study. Neuroimage. 2004;23:1450–1459. doi: 10.1016/j.neuroimage.2004.08.006. [DOI] [PubMed] [Google Scholar]
  • 93.Goekoop R, Scheltens P, Barkhof F, Rombouts SA. Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study. Brain. 2006;129:141–157. doi: 10.1093/brain/awh671. [DOI] [PubMed] [Google Scholar]
  • 94.Thiel CM. Cholinergic modulation of learning and memory in the human brain as detected with functional neuroimaging. Neurobiol Learn Mem. 2003;80:234–244. doi: 10.1016/s1074-7427(03)00076-5. [DOI] [PubMed] [Google Scholar]
  • 95.Tsukada H, Kakiuchi T, Ando I, Shizuno H, Nakanishi S, Ouchi Y. Regulation of cerebral blood flow response to somatosensory stimulation through the cholinergic system: a positron emission tomography study in unanesthetized monkeys. Brain Res. 1997;749:10–17. doi: 10.1016/s0006-8993(96)01028-1. [DOI] [PubMed] [Google Scholar]
  • 96.McGaughy J, Koene RA, Eichenbaum H, Hasselmo ME. Cholinergic deafferentation of the entorhinal cortex in rats impairs encoding of novel but not familiar stimuli in a delayed nonmatch-to-sample task. J Neurosci. 2005;25:10273–10281. doi: 10.1523/JNEUROSCI.2386-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.He Y, Wang L, Zang Y, et al. Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. Neuroimage. 2007;35:488–500. doi: 10.1016/j.neuroimage.2006.11.042. [DOI] [PubMed] [Google Scholar]
  • 98.Laufs H, Hamandi K, Salek-Haddadi A, Kleinschmidt AK, Duncan JS, Lemieux L. Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions. Hum Brain Mapp Nov 28, 2006 [Epub ahead of print]. [DOI] [PMC free article] [PubMed]
  • 99.Salek-Haddadi A, Diehl B, Hamandi K, et al. Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy. Brain Res. 2006;1088:148–166. doi: 10.1016/j.brainres.2006.02.098. [DOI] [PubMed] [Google Scholar]
  • 100.Fridman EA, Hanakawa T, Chung M, Hummel F, Leiguarda RC, Cohen LG. Reorganization of the human ipsilesional premotor cortex after stroke. Brain. 2004;127:747–758. doi: 10.1093/brain/awh082. [DOI] [PubMed] [Google Scholar]
  • 101.Katscher U, Bönert P. Parellel magnetic resonance imaging. Neurotherapeutics. 2007;4:498–509. [Google Scholar]
  • 102.Lutcke H, Merboldt KD, Frahm J. The cost of parallel imaging in functional MRI of the human brain. Magn Reson Imaging. 2006;24:1–5. doi: 10.1016/j.mri.2005.10.028. [DOI] [PubMed] [Google Scholar]
  • 103.Wiggins GC, Triantafyllou C, Potthast A, Reykowski A, Nittka M, Wald LL. 32-channel 3 Tesla receive-only phased-array head coil with soccer-ball element geometry. Magn Reson Med. 2006;56:216–223. doi: 10.1002/mrm.20925. [DOI] [PubMed] [Google Scholar]
  • 104.Kahn I, Wiggins CJ, Wiggins GC, et al. High-resolution 3T and 7T functional MRI: feasibility and specificity. Presented at the Society for Neuroscience; October 14, 2006; Atlanta.
  • 105.Dickerson BC, Wright CI, Miller S, et al. Ultrahigh-field differentiation of medial temporal lobe function: sub-millimeter fMRI of amygdala and hippocampal activation at 7 Tesla. Resented at the Organization for Human Brain Mapping; June 12, 2006; Florence.
  • 106.Miller KL, Smith SM, Jezzard P, Pauly JM. High-resolution FMRI at 1.5 T using balanced SSFP. Magn Reson Med. 2006;55:161–170. doi: 10.1002/mrm.20753. [DOI] [PubMed] [Google Scholar]
  • 107.Dickerson BC, Miller S, Greve DN, et al. Prefrontal-hippocampal-fusiform activity during encoding predicts intra-individual differences in free recall ability: An event-related functional-anatomic MRI study. Hippocampus; (in press). [DOI] [PMC free article] [PubMed]
  • 108.Cramer SC, Crafton KR. Somatotopy and movement representation sites following cortical stroke. Exp Brain Res. 2006;168:25–32. doi: 10.1007/s00221-005-0082-2. [DOI] [PubMed] [Google Scholar]
  • 109.Dickerson BC, Bakkour A, Salat DH, et al. The cortical signature of Alzheimer’s disease (AD): a high-throughput in vivo MRI-based quantitative biomarker. Presented at the 20th Annual Massachusetts Alzheimer’s Disease Research Center Symposium; January 11, 2007; Boston.

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