Mismatch negativity (MMN) is an auditory event-related potential (ERP) that reflects automatic stimulus discrimination in the human auditory system. By varying the interstimulus intervals (ISIs), the MMN can be used as an index of auditory sensory memory. This paper focuses on MMN findings in aging and in Alzheimer’s (AD) and Parkinson’s diseases (PD). The accumulated data suggest that MMN to duration deviance, unlike MMN to frequency deviance, is reduced in amplitude in aging at short ISIs. The attenuated MMN to frequency deviance observed at long ISIs in elderly subjects seems to be caused by age-related memory trace decay. Existing results suggest that automatic discrimination for the frequency change is not affected in the early phase of AD, whereas the memory trace seems to decay faster in AD patients. The present findings on PD are not as conclusive, although they tentatively suggest deteriorated automatic change detection. The MMN appears to offer an objective tool for studying auditory processing and memory trace decay in different neurological disorders.

Keywords:
Event-related potential (ERP), Mismatch negativity (MMN), Memory trace decay, Alzheimer’s disease, Parkinson’s disease, Aging, Magnetoencephalography (MEG)
1.
Adams RD, Victor M: The neurology of aging; in Adams DA, Virtor M (eds): Principles of Neurology. New York, McGraw-Hill, 1989, pp 488–497.
2.
Agid Y: Parkinson’s disease: Pathophysiology. Lancet 1980;337:1321–1324.
3.
Alho K: Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. Ear Hear 1995;16:38–50.
4.
Amenedo E, Diaz F: Automatic and effortful processes in auditory memory reflected by event-related potentials: Age-related findings. Electroencephalogr Clin Neurophysiol 1998;108:361–369.
5.
Anderson B, Rutledge V: Age and hemisphere effects on dendritic structure. Brain 1996;119:1983–1990.
6.
Baddeley AD: The psychology of memory; in Baddeley AD, Wilson BA, Watts FN (eds): Memory Disorders. Cambridge, Wiley, 1995, pp 3–25.
7.
Böttcher-Gandor C, Ullsperger P: Mismatch negativity in event-related potential to auditory stimuli as a function of varying interstimulus interval. Psychophysiology 1992;29:546–550.
8.
Csepe V, Molnar M: Towards the possible clinical application of the mismatch negativity component of event-related potentials. Audiol Neurootol 1997;2:354–369.
9.
Czigler I, Csibra G, Csontos A: Age and inter-stimulus interval effects on event-related potentials to frequent and infrequent auditory stimuli. Biol Psychology 1992;33:195–206.
10.
Deouell LY, Bentin S: Variable cerebral responses to equally distinct deviance in four auditory dimensions: A mismatch negativity study. Psychophysiology 1998;35:745–754.
11.
Escera C, Grau C: Short-term replicability of the mismatch negativity. Electroencephalogr Clin Neurophysiol 1996;100:549–554.
12.
Fischer C, Morlet D, Giard MH: Mismatch negativity and N100 in comatose patients. Audiol Neurootol 2000;5:192–197.
13.
Gaeta H, Friedman D, Ritter W, Cheng J: An event-related potential study of age-related changes in sensitivity. Neurobiol Aging 1998;19:447–459.
14.
Gaeta H, Friedman D, Ritter W, Cheng J: Changes in sensitivity to stimulus deviance in Alzheimer’s disease: An ERP perspective. Neuroreport 1999;10:281–287.
15.
Giard M-H, Perrin F, Pernier J, Bouchet P: Brain generators implicated in the processing of auditory stimulus deviance: A topographic event-related potential study. Psychophysiology 1990;27:627–640.
16.
Gunter TC, Jackson JL, Mulder G: Focussing on aging: An electrophysiological exploration of spatial and attentional processing during reading. Biol Psychol 1996;43:103–145.
17.
Halgren E, Marinkovic K, Chauvel P: Generators of the late cognitive potentials in auditory and visual oddball tasks. Electroencephalogr Clin Neurophysiol 1998;106:156–164.
18.
Hämäläinen M, Hari R, Ilmoniemi RJ, Knuutila J, Lounasmaa OV: Magnetoencephalography – Theory, instrumentation, and applications of noninvasive studies of the working human brain. Rev Mod Phys 1993;65:413–497.
19.
Hari R, Hämäläinen M, Ilmoniemi R, Kaukoranta E, Reinikainen K, Salminen J, Alho K, Näätänen R, Sams M: Responses of the primary auditory cortex to pitch changes in a sequence of tone pips. Neurosci Lett 1984;50:127–132.
20.
Hickish G: Hearing problem of elderly people. Br Med J 1989;299:1415–1416.
21.
Hoehn MD, Yahr MM: Parkinsonism: Onset, progression and mortality. Neurology 1967;17:427–442.
22.
Jääskeläinen IP, Varonen R, Näätänen R, Pekkonen E: Decay of cortical preattentive sound discrimination in middle-age. Neuroreport 1999;10:123–126.
23.
Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC: Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: Implication for schizophrenia. Proc Natl Acad Sci USA 1996;93:11962–11967.
24.
Joutsiniemi S-L, Ilvonen T, Sinkkonen J, Huotilainen M, Tervaniemi M, Lehtokoski A, Rinne T, Näätänen R: The mismatch negativity for duration decrement of auditory stimuli in healthy subjects. Electroencephalogr Clin Neurophysiol 1998;108:154–159.
25.
Kane NM, Butter SR, Simpson T: Coma outcome prediction using event-related potentials: P3 and mismatch negativity. Audiol Neurootol 2000;5:186–191.
26.
Kane NM, Curry SH, Rowland CA, Manara AR, Lewis T, Moss T, Cummins BH, Butler SR: Event-related potentials – Neurophysiological tools for predicting emergence and early outcome from traumatic coma. Intensive Care Med 1996;22:39–46.
27.
Karayanidis F, Andrews S, Ward PB, Michie PT: ERP indices of auditory selective attention in aging and Parkinson’s disease. Psychophysiology 1995;32:335–350.
28.
Kazmerski VA, Friedman D, Ritter W: Mismatch negativity during attend and ignore conditions in Alzheimer’s disease. Biol Psychiatry 1997;42:382–402.
29.
Kropotov JD, Näätänen R, SevostianovAV, Alho K, Reinikainen K, Kropotova OV: Mismatch negativity to auditory stimulus change recorded directly from the human temporal cortex. Psychophysiology 1995;32:418–422.
30.
Lang AH, Eerola O, Korpilahti P, Holopainen I, Salo S, Aaltonen O: Practical issues in the clinical application of mismatch negativity. Ear Hear 1995;16:118–130.
31.
Levänen S, Ahonen A, Hari R, McEvoy L, Sams M: Deviant auditory stimuli activate human left and right auditory cortex differently. Cerebr Cortex 1996;6:288–296.
32.
Luszcz MA, Bryan J: Toward understanding age-related memory loss in late adulthood. Gerontology 1999;45:2–9.
33.
Morlet D, Bouchet P, Fischer C: Mismatch negativity and N100 monitoring: Potential clinical value and methodological advances. Audiol Neurootol 2000;5:198–206.
34.
Näätänen R: Attention and Brain Function. New Jersey, Hillsdale, Erlbaum, 1992.
35.
Näätänen R: The mismatch negativity: A powerful tool for cognitive neuroscience. Ear Hearing 1995;16:6–18
36.
Namba H, Iyo M, Shinotoh H, Nagatsuka S, Fukushi K, Irie T: Preserved acetylcholinesterase activity in aged cerebral cortex. Lancet 1998;351:881–882.
37.
Pekkonen E, Jousmäki V, Könönen M, Reinikainen K, Partanen J: Auditory sensory memory impairment in Alzheimer’s disease: An event-related potential study. Neuroreport 1994;5:2537–2540.
38.
Pekkonen E, Jousmäki V, Partanen K, Karhu J: Mismatch negativity area and age-related auditory memory. Electroencephalogr Clin Neurophysiol 1993;87:321–325.
39.
Pekkonen E, Jousmäki V, Reinikainen K, Partanen J: Automatic auditory discrimination is impaired in Parkinson’s disease. Electroencephalogr Clin Neurophysiol 1995a;95:47–52.
40.
Pekkonen E, Rinne T, Näätänen R: Variability and replicability of the mismatch negativity. Electroencephalogr Clin Neurophysiol 1995b;96:546–554.
41.
Pekkonen E, Rinne T, Reinikainen K, Kujala T, Alho K, Näätänen R: Aging effects on auditory processing: An event-related potential study. Exp Aging Res 1996;22:171–184.
42.
Pirch JH: Electrophysiological effects of acetylcholine on central neurons (whole cells and interactions); in Stone TW (ed): CNS Neurotransmitters and Neuromodulators: Acetylcholine. Boca Raton, CRC Press, 1995, pp 115–128.
43.
Richards T: Ageing costs. Br Med J 1998;317:896.
44.
Riekkinen P Jr, Pääkönen A, Karhu J, Partanen J, Soininen H, Laakso M, Riekkinen P Sr: THA disrupts mismatch negativity in Alzheimer’s disease. Psychopharmacology 1997;133:203–206.
45.
Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT, the Donepezil Study Group: A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 1998;50:136–145.
46.
Sams M, Hari R, Rif J, Knuutila J: The human auditory sensory memory trace persists about 10 sec: Neuromagnetic evidence. J Cogn Neurosci 1993;3:363–370.
47.
Schapira AHV: Parkinson’s disease. Br Med J 1999;318:311–314.
48.
Schroeder MM, Ritter W, Vaughan HG Jr: The mismatch negativity to novel stimuli reflects cognitive decline; in Grafman J, Holyoak KJ (eds): Structure and Functions of the Prefrontal Cortex. New York, Annals New York Acad Sciences, 1995, vol 769, pp 399–401.
49.
Schröger E: The influence of stimulus intensity and inter-stimulus interval on the detection of pitch and loudness changes. Electroencephalogr Clin Neurophysiol 1996;100:517–526.
50.
Sinha UK, Hollen KM, Rodrigues R, Miller CA: Auditory system degeneration in Alzheimer’s disease. Neurology 1993;43:779–785.
51.
Squire LR, Zola-Morgan S: The medial temporal lobe memory system. Science 1991;253:1380–1386.
52.
Stam CJ, Visser SL, Op de Coul AAW, De Sonneville LMJ, Schellens RLL, Brunia CHM, de Smet JS, Gielen G: Disturbed frontal regulation of attention in Parkinson’s disease. Brain 1993;116:1139–1158.
53.
Terry RD, Katzman R, Bick KL: Alzheimer Disease. New York, Raven Press, 1994.
54.
Testa JA, Brumback RA, Baik T-K, Leech RW, Cannon T: Neuropathology and memory dysfunction in neurodegenerative disease; in Tröster AI (ed): Memory in Neurodegenerative Disease. Cambridge, Cambridge University Press, 1998, pp 36–86.
55.
Verleger R, Kömpf D, Neukäter W: Event-related potentials in mild dementia of the Alzheimer’s type. Electroencephalogr Clin Neurophysiol 1992;84:332–343.
56.
Verleger R, Neukäter W, Kömpf D, Vieregge P: On the reasons for the delay of P3 latency in healthy elderly subjects. Electroencephalogr Clin Neurophysiol 1991;79:488–502.
57.
Vieregge P, Verleger R, Wascher E, Stuven F, Kömpf D: Auditory selective attention is impaired in Parkinson disease – Event-related evidence from EEG potentials. Cogn Brain Res 1994;2:117–129.
58.
Woods DL: Auditory selective attention in middle-aged and elderly subjects: An event-related potential study. Electroencephalogr Clin Neurophysiol 1992;84:456–468.
59.
Yokoyama Y, Nakashima K, Shimoyama R, Urakami K, Takahashi K: Distribution of event-related potentials in patients with dementia. Electromyogr Clin Neurophysiol 1995;35:431–437.
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