History and future directions of human brain mapping and functional neuroimaging

Acta Psychologica

Volumn 107, Issue 1-3, 2001, Pages 9-42

  Savoy, Robert L ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

Brain mapping; EEG; fMRI; MEG; PET; TMS

Indexed keywords

ANATOMY; ARTICLE; BRAIN; BRAIN MAPPING; COMPUTER ASSISTED EMISSION TOMOGRAPHY; DIAGNOSTIC IMAGING; ELECTROENCEPHALOGRAPHY; FORECASTING; HEMODYNAMICS; HISTOLOGY; HISTORY; MAGNETISM; NEUROPHYSIOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; PHYSIOLOGY; VASCULARIZATION;

ANATOMY; BRAIN; BRAIN MAPPING; DIAGNOSTIC IMAGING; ELECTROENCEPHALOGRAPHY; FORECASTING; HEMODYNAMIC PROCESSES; HISTORY, 20TH CENTURY; MAGNETIC RESONANCE IMAGING; MAGNETICS; NEUROPHYSIOLOGY; TOMOGRAPHY, EMISSION-COMPUTED;

EID: 0035316933     PISSN: 00016918     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0001-6918(01)00018-X     Document Type: Article

References (104)

1. Adams, R. D., & Victor, M. (1985). Principles of neurology (3rd ed., Vol. Part 1/Approach to the Patient with Neurological Disease). New York: McGraw-Hill.
2. Aguirre, G. K., Zarahn, E., & D'Esposito, M. (1998). The variability of human BOLD hemodynamic responses. Neurolmage, 8, 360-369.
3. Bandettini, P. A., Birn, R. M., & Donahue, K. M. (2000). Functional MRI: background, methodology, limits, and implementation. In J. T. Cacioppo, L. G. Tassinary, & G. G. Berntson (Eds.), Handbook of psychophysiology (2nd ed., pp. 978-1014). Cambridge, UK: Cambridge University Press.
4. Basser, P. J., Pajevic, S., Pierpaoli, C., Duda, J., & Aldroubi, A. (2000). In vivo fiber tractography using DT-MRI data. Magnetic Resonance in Medicine, 44(4), 625-632.
5. Birn, R. M., Bandettini, P. A., Cox, R. W., & Shaker, R. (1999). Event-related fMRI of tasks involving brief motion. Human Brain Mapping, 7(2), 106-114.
6. Bonhoeffer, T., & Grinvald, A. (1996). Optical imaging based on intrinsic signals: the methodology. In A. W. Toga, & J. C. Mazziotta (Eds.), Brain mapping: The methods (pp. 55-97). San Diego: Academic Press.
7. Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (in press). Conflict monitoring and cognitive control.
8. Boynton, G. M., Engel, S. A., Glover, G. H., & Heeger, D. J. (1996). Linear systems analysis of functional magnetic resonance imaging in human V1. Journal of Neuroscience, 16(13), 4207-4221.
9. Brandt, S. A., Brocke, J., Niehaus, L., Röricht, A., Villringer, A., & Meyer, B.-U. (1999). Distant effects from transcranial electrical stimulation (TES) over motor cortex during fMRI. Paper presented at the Fifth International Conference on Functional Mapping of the Human Brain, Düsseldorf, Germany.
10. Brazier, M. A. B. (1961). A history of the electrical activity of the brain: The first half-century. London: Pitman Medical Publishing.
11. Brazier, M. A. B. (1988). A history of neurophysiology in the 19th century. New York: Raven Books.
12. Breiter, H. C., Gollub, R. L., Weisskoff, R. M., Kennedy, D. N., Makris, N., Berke, J. D., Goodman, J. M., Kantor, H. L., Gastfriend, D. R., Riorden, J. P., Mathew, R. T., Rosen, B. R., & Hyman, S. E. (1997). Acute effects of cocaine on human brain activity and emotion. Neuron, 19(9), 591-611.
13. Brewer, J. B., Zhao, Z., Desond, J. E., Glover, G. H., & Gabrieli, J. D. E. (1998). Making memories: brain activity that predict show well visual experience will be remembered. Science, 281, 1185-1187.
14. Buckner, R. L., Bandettini, P. A., O'Craven, K. M., Savoy, R. L., Petersen, S. E., Raichle, M. E., & Rosen, B. R. (1996). Detection of cortical activation during averaged single trials of a cognitive task using functional magnetic resonance imaging. Proceedings of the National Academy of Science, 93, 14878-14883.
15. Bushong, S. C. (1995). Magnetic resonance imaging: Physical and biological principles. Boston: Mosby-Year Book.
16. Buxton, R. B., Wong, E. C., & Frank, L. R. (1999). The post-stimulus undershoot of the functional MRI signal. In C. T. W. Moonen, & A. Bandettini (Eds.), Functional MRI (pp. 253-262). Berlin: Springer.
17. Cabeza, R., & Nyberg, L. (1997). Imaging cognition: an empirical review of PET studies with normal subjects. Journal of Cognitive Neuroscience, 9, 1-26.
18. Cabeza, R., & Nyberg, L. (2000). Imaging cognition II: an empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12, 1-47.
19. Calvin, W. H., & Ojemann, G. A. (1995). Conversations with Neil's brain: The neural nature of thought and language. Reading, MA: Perseus Publishing.
20. Carter, C. S., Braver, T. S., Barch, D. M., Botvinick, M. M., Noll, D., & Cohen, J. D. (1998). Anterior cingulate cortex, error detection, and the online monitoring of performance. Science, 280, 747-749.
21. Chen, K., Perelman, L. T., Zhang, Q., Dasari, R. R., & Feld, M. S. (2000). Optical computed tomography in a turbid medium using early arriving photons. Journal of Biomedical Optics, 5, 144-154.
22. Cheng, K., Waggoner, R. A., & Tanaka, K. (1999). Patterns of human ocular dominance columns as revealed by high-field (4T) magnetic resonance imaging (FMRI). Paper presented at the Annual Meeting of the Society for Neuroscience, Miami Beach, FL, USA.
23. Cherry, S. R., & Phelps, M. E. (1996). Imaging brain function with positron emission tomography. In A. W. Toga, & J. C. Mazziotta (Eds.), Brain mapping: the methods (pp. 191-221). San Diego: Academic Press.
24. Clarke, J. (1994). SQUIDs. Scientific American, (August), 46-53.
25. Corbetta, M., Miezin, F. M., Dobmeyer, S., Shulman, G. L., & Petersen, S. E. (1990). Attentional modulation of neutral processing of shape, color, and velocity in humans. Science, 248, 1556-1559.
26. Corkin, S., Amaral, D. G., Johnson, K. A., & Hyman, B. T. (1997). H.M.'s medial temporal lobe lesion: findings from MRI. Journal of Neuroscience, 17, 3964-3979.
27. Culham, J. C., Dukelow, S. P., Vilis, T., Hassard, F. A., J.S, , Menon, R. S., & Goodale, M. A. (1999). Recovery of fMRI activation in motion area MT following storage of the motion after effect. Journal of Neurophysiology, 81, 388-393.
28. Culham, J., He, S., Dukelow, S., & Verstraten, F. (2001). Visual motion and the human brain: what has neuroimaging told us?. Acta Psychologica, 107, 69-94.
29. Dale, A. M., & Buckner, R. L. (1997). Selective averaging of rapidly presented individual trials using fMRI. Human Brain Mapping, 5, 329-340.
30. Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis: I. Segmentation and surface reconstruction. Neurolmage, 9, 179-194.
31. Dale, A. M., Liu, A. K., Fischl, B. R., Buckner, R. L., Belliveau, J. W., Lewine, J. D., & Halgren, E. (2000). Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity. Neuron, 26, 55-67.
32. Dale, A. M., & Sereno, M. I. (1993). Improved localization of cortical activity by combining EEG and MEG with MRI cortical surface reconstruction: a linear approach. Journal of Cognitive Neuorscience, 5(2), 162-176.
33. Drury, H. A., Van Essen, D. C., Anderson, C. H., Lee, C. W., Coogan, T. A., & Lewis, J. W. (1996). Computerized mappings of the cerebral cortex: a multiresolution flattening method and a surface-based coordinate system. Journal of Cognitive Neuroscience, 8, 1-28.
34. Edward, V., Windischberger, C., Cunnington, R., Lanzenberger, R., Erdler, M., Mayer, D., Endl, W., & Beisteiner, R. (2000). Qualification of fMRI artifact reduction by a novel plaster case headholder. Human Brain Mapping, 11, 207-213.
35. Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis: II. Inflation, flattening, and a surface-based coordinate system. Neurolmage, 9, 195-207.
36. Fletcher, P. C., Frith, C. D., Grasby, P. M., Shallice, T., Frackowiak, R. S. J., & Dolan, R. J. (1995). Brain systems for encoding and retrieval of auditory-verbal memory. Brain, 118, 401-416.
37. Foltys, H., Kemeny, S., Krings, T., Boroojerdi, B., Sparing, R., Thron, A., & Topper, R. (2000). The representation of the plegic hand in the motor cortex: a combined fMRI and TMS study. NeuroReport, 11(1), 147-150.
38. Fox, P. T., & Raichle, M. E. (1986). Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proceedings of the National Academy of Science, USA, 83(4), 1140-1144.
39. Frostig, R. D., Lieke, E. E., Ts'o, D. Y., & Grinvald, A. (1990). Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proceedings of the National Academy of Science, USA, 87(16), 6082-6086.
40. Fulton, J. F. (1928). Observations upon the vascularity of the human occiptial lobe during visual activity. Brain, 51, 310-320.
41. George, M. S., Lisanby, S. H., & Sackeim, H. A. (1999). Transcranial magnetic stimulation: applications in neuropsychiatry. Archives of General Psychiatry, 56, 300-311.
42. Gevins, A. (1996). Electrophysiological imaging of brain function. In A. W. Toga, & J. C. Mazziotta (Eds.), Brain mapping: the methods (pp. 259-276). San Diego: Academic Press.
43. Gollub, R. L., Breiter, H. C., Kantor, H., Kennedy, D., Gastfriend, D., Mathew, R. T., Markis, N., Guimaraes, A., Riorden, J., Campbell, T., Foley, M., Hyman, S. E., Rosen, B., & Weisskoff, R. (1998). Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects. Journal of Cerebral Blood Flow and Metabolism, 18, 724-734.
44. Gratton, G., & Fabiani, M. (1998). Dynamic brain imaging: event-related optical signal (EROS) measures of the time course and localization of cognitive-related activity. Psychonomic Bulletin Review, 5(4), 535-563.
45. Gratton, G., Maier, J. S., Fabiani, M., Mantulin, W. W., & Gratton, E. (1994). Feasibility of intra-cranial near-infrared optical scanning. Psychophysiology, 31(2), 211-215.
46. Halgren, E., Walter, R. D., Cherlow, D. G., & Crandall, P. H. (1978). Mental phenomena evoked by electrical stimulation of the human hippocampal formation and amygdala. Brain, 101, 83-117.
47. He, S., Cohen, E. R., & Hu, X. (1998). Close correlation between activity in brain area MT/V5 and the perception of a visual motion after effect. Current Biology, 8, 1215-1218.
48. Hu, X., Yacoub, E., Le, T. H., Cohen, E. R., & Ugurbil, K. (1999). Functional MRI signal decrease at the onset of stimulation. In C. T. W. Moonen, & P. A. Bandettini (Eds.), Functional MRI (pp. 244-252). Berlin: Springler.
49. Ishai, A., Ungerleider, L. G., Martin, A., Shouten, J. L., & Haxby, J. V. (1999). Distributed representation of objects in the human ventral visual pathway. Proceedings of the National Academy of Sciences, USA, 96, 9379-9384.
50. Jennings, C., & Aamodt, S. (2000). Computational approaches to brain function. Nature Neuroscience, 3(Supplement), 1160.
51. Kim, S. -G., Lee, S. P., Goodyear, B., & Silva, A. C. (1999). Spatial resolution of BOLD and other fMRI techniques. In C. T. W. Moonen, & P. A. Bandettini (Eds.), Functional MRI (pp. 195-203). Berlin: Springer.
52. Kingberg, T., Hedehus, M., Temple, E., Salz, T., Gabrieli, J. D. E., Moseley, M. E., & Poldrack, R. A. (2000). Microstructure of temporo-parietal white matter as a basis for reading ability: evidence from diffusion tensor magnetic resonance imaging. Neuron, 25, 493-500.
53. Kolb, B., & Whishaw, I. Q. (1996). Fundamentals of human neuropsychology (4th ed.). New York: Freeman.
54. Kosslyn, S. M., Andersen, R. A. (Eds.), Frontiers in cognitive neuroscience. Cambridge: The MIT Press.
55. Kwong, K. K., Belliveau, J. W., Chesler, D. A., Goldberg, I. E., Weisskoff, R. M., Poncelet, B. P., Kennedy, D. N., Hoppel, B. E., Cohen, M. S., Turner, R., Cheng, H.-M., Brady, T. J., & Rosen, B. R. (1992). Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proceedings of the National Academy of Sciences, 89, 5675-5679.
56. Lewine, J. D., & Orrison, W. W. J. (1995a). Clinical electroencephalography and event-related potentials, In W. W. J. Orrison, J. D. Lewine, J. A. Sanders, & M. F. Hartshorne (Eds.), Functional brain imaging (pp. 327-368). Boston: Mosby-Year Book.
57. Lewine, J. D., & Orrison, W. W. J. (1995b). Magnetoenecephalography and magnetic source imaging. In W. W. J. Orrison, J. D. Lewine, J. A. Sanders, & M. F. Hartshorne (Eds.), Functional brain imaging (pp. 369-418). Boston: Mosby-Year Book.
58. Lounasmaa, O. V., Hämäläinen, M., Hari, R., & Salmelin, R. (1996). Information processing in the human brain: magnetoencephalographic approach. Proceedings of the National Academy of Science, USA, 93, 8809-8815.
59. Makris, N., Worth, A. J., Sorensen, A. G., Papadimitriou, G. M., Wu, O., Reese, T. G., Wedeen, V. J., Davis, T. L., Stakes, J. W., V.S, , Kaplan, E., Rosen, B. R., Pandya, D. N., & Kennedy, D. N. (1997). Morphometry of in vivo human white matter association pathways with diffusion-weighted magnetic resonance imaging. Annals of Neurology, 42(6), 951-962.
60. Malonek, D., & Grinvald, A. (1996). Interactions between electrical activity cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science, 272, 551-554.
61. McIntosh, A. R. (1999). Mapping cognition to the brain through neural interactions. Memory, 7(5/6), 523-548.
62. Meehl, P. E. (1967). Theory-testing in psychology and physics: a methodological paradox. Philosophy of Science, 34(2), 103-115.
63. Mel, B. W. (2000). In the brain, the model is the goal. Nature Neuroscience, 3 (Supplement), 1183.
64. Menon, R. S., Ogawa, S., Strupp, J. P., & Urgurbil, K. (1997). Mapping ocular dominance columns in human V1 using fMRI. Journal of Neurophysiology, 77, 2780-2787.
65. Moonen, C. T. W., Bandettini, P. A. (Eds.), Functional MRI. Berlin: Spingler.
66. Moore, C., & Engel, S. A. (1999). Visual perception: mind and brain see eye to eye. Current Biology, 9, R74-R76.
67. Morris, J. S., Friston, K. J., Buchel, C., Frith, C. D., Young, A. W., Calder, A. J., & Dolan, R. J. (1998). A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain, 121(Part 1), 47-57.
68. Mosso, A. (1881). Ueber den Kreislauf des Blutes im Menschlichen Gehirn [Concerning the circulation of the blood in the human brain]. Leipzig: Verlag von Veit & Company.
69. Ojemann, J. G., Buckner, R. L., Akbudak, E., Snyder, A. Z., Ollinger, J. M., McKinstry, R. C., Rosen, B. R., Petersen, S. E., Raichle, M. E., & Conturo, T. E. (1998). Functional MRI studies of word-stem completion: reliability across laboratories and comparison to blood flow imaging with PET. Human Brain Mapping, 6(4), 203-215.
70. Pascual-Leone, A., Bartres-Faz, D., & Keenan, J. P. (1999). Transcranial magnetic stimulation: studying the brain-behavior relationship by induction of 'virtual lesions'. Philosophical Transactions of the Royal Society of London B, 354, 1229-1238.
71. Pascual-Leone, A., & Meador, K. J. (1998). Is transcranial magnetic stimulation coming of age? Journal of Clinical Neurophysiology, 15(4), 285-287.
72. Pascual-Leone, A., Tormos, J. M., Keenan, J., Tarazona, F., Cañete, C., & Catalá, M. D. (1998). Study and modulation of human cortical excitability with transcranial magnetic stimulation. Journal of Clinical Neurophysiology, 15(4), 333-343.
73. Pascual-Leone, A., Walsh, V., & Rothwell, J. (2000). Transcranial magnetic stimulation in cognitive neuroscience-virtual lesion, chronometry, and functional connectivity. Current Opinion in Neurobiology, 10, 232-237.
74. Paus, T. (1999). Imaging the brain before, during, and after transcranial magnetic stimulation. Neuropsychologia, 37(2), 219-224.
75. Paus, T., & Wolforth, M. (1998). Transcranial magnetic stimulation during PET: reaching and verifying the target site. Human Brain Mapping, 6(5&6), 399-402.
76. Penfield, W., & Jasper, H. (1954). Epilepsy and the functional anatomy of the human brain. Boston: Little, Brown and Company.
77. Petersen, S. E., Fox, P. T., Posner, M. I., Minton, M., & Raichle, M. E. (1988). Positron emission tomographic studies of the cortical anatomy of single-word processing. Nature, 331, 585-589.
78. Polyak, S. (1957). The vetebrate visual system. Chicago: The University of Chicago Press.
79. Puce, A., Constable, R. T., Luby, M. L., McCarthy, G., Nobre, A. C., Spencer, D. D., Gore, J. C., & Allison, T. (1995). Functional magnetic resonance imaging of sensory and motor cortex: comparison with electrophysiological localization. Journal of Neurosurgery, 83(2), 262-270.
80. Raichle, M. E. (1998). Behind the scenes in functional brains imaging: a historical and physiological perspective. Proceedings of the National Academy of Sciences, USA, 95, 765-772.
81. Raichle, M. E. (2000). A brief history of human functional brain mapping. In A. W. Toga, & J. C. Mazziotta (Eds.), Brain mapping: The systems (pp. 33-75). San Diego: Academic Press.
82. Richter, W., Somorjai, R., Summers, R., Jarmasz, M., Menon, R. S., Gati, J. S., Georgopoulos, A. P., Tegeler, C., Ugurbil, K. S., & Kim, S.-G. (2000). Motor area activity during mental rotation studied by time-resolved single-trial fMRI. Journal of Cognitive Neuroscience, 12(2), 310-320.
83. Rosen, B. R., Buckner, R. L., & Dale, A. M. (1998). Event-related functional MRI: past, present, and future. Proceedings of the National Academy of Sciences, 95, 773-780.
84. Roy, C. S., & Sherrington, C. S. (1890). On the regulation of the blood-supply of the brain. Journal of Physiology, 11, 85-108.
85. Savoy, R. L., Bandettini, P. A., O'Craven, K. M., Kwong, K. K., Davis, T. L., Baker, J. R., Weisskoff, R. M., & Rosen, B. R. (1995). Pushing the temporal resolution of fMRI: studies of very brief visual stimuli, onset variability and asynchrony, and stimulus-correlated changes in noise. In Proceedings of the International Society of Magnetic Resonance in Medicine, Third Scientific Meeting, Vol. 2. p. 450.
86. Savoy, R. L., O'Craven, K. M., Weisskoff, R. M., Davis, T. L., Baker, J. R., & Rosen, B. R. (1994). Exploring the temporal resolution boundaries of fMRI: measuring responses to very brief visual stimuli. Paper presented at the Annual Meeting of the Society for Neuroscience, Miami Beach, FL.
87. Savoy, R. L., Ravicz, M. E., & Gollub, R. (1999). The psychophysiological laboratory in the magnet: stimulus delivery, response recording, and safety. In C. T. W. Moonen, & P. A. Bandettini (Eds.), Functional MRI (pp. 347-365). Berlin: Springer.
88. Schacter, D. L., Buckner, R. L., Koutstaal, W., Dale, A., & Rosen, B. (1997). Late onset of anterior prefrontal activity during true and false recognition: an event-related fMRI study. Neurolmage, 6, 259-269.
89. Sereno, M. I., Dale, A. M., Reppas, J. B., Kwong, K. K., elliveau, J. W., Brady, T. J., Rosen, B. R., & Tootell, R. B. H. (1995). Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. Science, 268(May 12), 889-893.
90. Shellock, F. G., & Kanal, E. (1996). Magnetic resonance: bioeffects, safety, and patient management (2nd edn). New York: Lippincott-Raven.
91. Song, A. W., & Takahashi, A. M. (2000). Displacement encoded imaging of small electric current. Paper presented at the ISMRM: International Society for Magnetic Resonance in Medicine, Denver, Colorado, USA.
92. Stevens, C. F. (2000). Models are common; good theories are scarce. Nature Neuroscience, 3(Supplement), 1177.
93. Stewart, L., Ellison, A., Walsh, V., & Cowey, A. (2001). The role of Transcranial Magnetic Stimulation (TMS) in studies of vision, attention and cognition. Acta Psychologica, 107, 275-291.
94. Swartz, B. E., & Goldensohn, E. S. (1998). Timeline of the history of EEG and associated fields. Electroencephalography and Clinical Neurophysiology, 106, 173-176.
95. Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain. New York: Thieme Medical Publishers.
96. Tootell, R. B. H., Dale, A. M., Sereno, M. I., & Malach, R. (1996). New images from human visual cortex. Trends in Neuroscience, 19(11), 481-489.
97. Tootell, R. B. H., Reppas, J. B., Dale, A. M., Look, R. B., Sereno, M. I., Malach, R., Brady, T. J., & Rosen, B. R. (1995). Visual motion after effect in human cortical area MT revealed by functional magnetic resonance imaging. Nature, 375(May 11), 139-141.
98. Tuch, D. S., Wedeen, V. J., Dale, A. M., George, J. S., & Belliveau, J. W. (1999). Conductivity mapping of biological tissue using diffusion MRI. Annals of the New York Academy of Science, 888, 314-316.
99. Vignal, J. P., Chauvel, P., & Halgren, E. (2000). Localised face processing by the human prefrontal cortex: stimulation-evoked hallucinations ef faces. Cognitive Neuropsychology, 17, 281-291.
100. Villringer, A. (1999). Physiological changes during brain activation. In C. T. W. Moonen, & P. A. Bandettini (Eds.), Functional MRI (pp. 3-13). Berlin: Springer.
101. Villringer, A., & Chance, B. (1997). Non-invasive optical spectroscopy and imaging of human brain function. Trends in Neuroscience, 20(10), 435-442.
102. Wagner, A. D., Schacter, D. L., Rotte, M., Koutstaal, W., Maril, A., Dale, A. M., Rosen, B. R., & Buckner, R. L. (1998). Building memories: remembering and forgetting of verbal experiences as predicted by brain activity. Science, 281, 1188-1191.
103. Walsh, V., & Cowey, A. (1998). Magnetic stimulation studies of visual cognition. Trends in Cognitive Neuroscience, 2(3), 103-110.
104. Wong, E. C., & Bandettini, P. A. (1999). Simultaneous acquisition of multiple forms of fMRI contrast. In C. T. W. Moonen, & P. A. Bandettini (Eds.), Functional MRI (pp. 183-192). Berlin: Springer.