Cholinergic modulation of preattentive auditory processing in aging
Abstract
Auditory event-related potential (ERP) components P50 and N100 are thought to index preattentive auditory processing underlying stimulus detection, whereas a subsequent component termed mismatch negativity (MMN) has been proposed to reflect comparison of incoming stimuli to a short-lived sensory memory trace of preceding sounds. Existing evidence suggests impairment of preattentive auditory processing in aging, which appears to be accompanied by decline of cholinergic activity. Previous studies indicate that scopolamine, which is a centrally acting muscarinic receptor antagonist, modulates preattentive auditory processing in young subjects. It has remained elusive, however, to which extent scopolamine affects preattentive auditory processing in aged subjects. We measured auditory responses simultaneously with electroencephalogram (EEG) and magnetoencephalogram (MEG) from nine non-demented elderly subjects after intravenous injection of scopolamine or glycopyrrolate, the latter being a peripherally acting cholinergic antagonist, using a double blind protocol. Scopolamine significantly delayed electric P50, both electric and magnetic N100 responses, whereas subsequent MMN and P200 responses were not altered by scopolamine. Our results indicate that the cholinergic system modulates auditory processing underlying stimulus detection in aging. In addition, auditory evoked responses appear to have different age-related sensitivity to cholinergic modulation. The combined MEG/EEG measurements using particularly auditory N100 response might offer an objective tool to monitor cholinergic activity in aging and Alzheimer's disease (AD).
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 cholinergic deficit in AD is one mechanism by which cortical generators of the neurophysiological response may differ.
“The cholinergic deficit in AD is one mechanism by which cortical generators of the neurophysiological response may differ.”
From Alzheimer's disease and its progression reduce pyramidal cell gain and connectivity (2025) · cites this paper as [39]
Mismatch negativity responses are altered by cholinergic antagonists and by deep brain stimulation of the nucleus basalis of Meynert.
“For example, mismatch negativity responses are altered by cholinergic antagonists 39 and by deep brain stimulation of the nucleus basalis of Meynert, a major source of cholinergic innervation of the cortex. 40”
From Alzheimer's disease and its progression reduce pyramidal cell gain and connectivity (2025) · cites this paper as [39]
Cites
Hämäläinen, M., Hari, R., Ilmoniemi, R. J., Knuutila, J., & Lounasmaa, O. V. (1993) · Reviews of Modern Physics · doi:10.1103/revmodphys.65.413 · Cited by 4,684 · see citing works
Risto, N. (2018) · Routledge eBooks · doi:10.4324/9780429487354 · Cited by 2,035 · see citing works
Wijers, B. (1995) · Acta Psychologica · doi:10.1016/0001-6918(95)90043-8 · Cited by 1,319 · see citing works
Effects of aging on event‐related brain potentials and reaction times in an auditory oddball task
Iragui, V. J., Kutas, M., MITCHINER, M. R., & Hillyard, S. A. (1993) · Psychophysiology · doi:10.1111/j.1469-8986.1993.tb03200.x · Cited by 233 · see citing works
Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model
Molchan, S. E., Martínez, R. A., Hill, J., Weingartner, H. J., Thompson, K., Vitiello, B., & Sunderland, T. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90017-g · Cited by 184 · see citing works
Brain Events Underlying Detection and Recognition of Weak Sensory Signals
Parasuraman, R., & Beatty, J. (1980) · Science · doi:10.1126/science.7414324 · Cited by 176 · see citing works
Mismatch Negativity in Aging and in Alzheimer’s and Parkinson’s Diseases
Pekkonen, E. (2000) · Audiology and Neurotology · doi:10.1159/000013883 · Cited by 157 · see citing works
Self-citationBertoli, S., Smurzyński, J., & Probst, R. R. (2002) · Clinical Neurophysiology · doi:10.1016/s1388-2457(02)00013-5 · Cited by 144 · see citing works
Midlatency auditory evoked responses: differential effects of a cholinergic agonist and antagonist
Buchwald, J. S., Rubinstein, E. H., Schwafel, J., et al. (1991) · Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section · doi:10.1016/0168-5597(91)90114-d · Cited by 109 · see citing works
Frechilla, D., Cobreros, A., Saldise, L., Moratalla, R., Insausti, R., Luquín, M. R., & R�o, J. D. (2001) · Synapse · doi:10.1002/1098-2396(20010315)39:4 · Cited by 103 · see citing works
Auditory Sensory Memory and the Cholinergic System: Implications for Alzheimer's Disease
Pekkonen, E., Hirvonen, J., Jääskeläinen, I. P., Kaakkola, S., & Huttunen, J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0805 · Cited by 102 · see citing works
Self-citationHypersensitivity to scopolamine in the elderly
Flicker, C., Ferris, S. H., & Serby, M. (1992) · Psychopharmacology · doi:10.1007/bf02245172 · Cited by 100 · see citing works
Midlatency auditory evoked responses: differential abnormality of P1 in Alzheimer's disease
Buchwald, J. S., Erwin, R. J., Read, S., Lancker, D. V., & Cummings, J. L. (1989) · Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section · doi:10.1016/0168-5597(89)90005-1 · Cited by 95 · see citing works
Age-related functional differences between auditory cortices
Pekkonen, E., Huotilainen, M., Virtanen, J. P., et al. (1995) · Neuroreport · doi:10.1097/00001756-199509000-00023 · Cited by 77 · see citing works
Self-citationCentral Anticholinergic Hypersensitivity in Aging
Ray, P. G., Meador, K. J., Loring, D. W., Zamrini, E. W., Yang, X., & Buccafusco, J. J. (1992) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/002383099200500203 · Cited by 74 · see citing works
Effects of aging on middle-latency auditory evoked potentials: A cross-sectional study
Amenedo, E., & Dı́az, F. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00255-2 · Cited by 70 · see citing works
Event-related potential changes in healthy aged females
Pfefferbaum, A., Ford, J. M., Roth, W. T., Hopkins, W. F., & Kopell, B. S. (1979) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(79)90052-x · Cited by 65 · see citing works
Age-related decline in central cholinergic function demonstrated with scopolamine
Tariot, P. N., Patel, S., Cox, C., & Henderson, R. E. (1996) · Psychopharmacology · doi:10.1007/bf02247392 · Cited by 61 · see citing works
Early Diagnosis of Alzheimer’s Disease
Daffner, K. R., & Scinto, L. F. M. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-005-6_1 · Cited by 56 · see citing works
Ageing-related changes in the processing of attended and unattended standard stimuli
Amenedo, E., & Dı́az, F. (1999) · Neuroreport · doi:10.1097/00001756-199908020-00030 · Cited by 52 · see citing works
Impaired preconscious auditory processing and cognitive functions in Alzheimer's disease
Pekkonen, E., Jääskeläinen, I. P., Hietanen, M., Huotilainen, M., Näätänen, R., Ilmoniemi, R. J., & Erkinjuntti, T. (1999) · Clinical Neurophysiology · doi:10.1016/s1388-2457(99)00153-4 · Cited by 47 · see citing works
Self-citationEngeland, C. G., Mahoney, C., Mohr, E., Ilivitsky, V., & Knott, V. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00711-6 · Cited by 37 · see citing works
Preserved acetylcholinesterase activity in aged cerebral cortex
Namba, H., lyo, M., Shinotoh, H., Nagatsuka, S.-I., Fukushi, K., & Irie, T. (1998) · The Lancet · doi:10.1016/s0140-6736(05)70293-2 · Cited by 36 · see citing works
The middle latency auditory evoked potential may be abnormal in dementia
Green, J. B., Flagg, L., Freed, D. M., et al. (1992) · Neurology · doi:10.1212/wnl.42.5.1034 · Cited by 32 · see citing works
Ninomiya, H., Onitsuka, T., Chen, C.-H., et al. (1997) · Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section · doi:10.1016/s0168-5597(96)96026-8 · Cited by 28 · see citing works
Green, J. B., Burba, A., Freed, D. M., et al. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199709000-00007 · Cited by 28 · see citing works
Synergistic anticholinergic and antiserotonergic effects in humans
Meador, K. J., Loring, D. W., Hendrix, N., et al. (1995) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688639508405149 · Cited by 27 · see citing works
Aging effects on auditory middle latency responses.
Azumi, T., Nakashima, K., & Takahashi, K. (1995) · PubMed · Cited by 27 · see citing works
Early Diagnosis of Alzheimer's Disease
Scinto, L. F. M., & Daffner, K. R. (2000) · Humana Press eBooks · doi:10.1385/1592590055 · Cited by 25 · see citing works
Scopolamine enhances middle-latency auditory evoked magnetic fields
Jääskeläinen, I. P., Hirvonen, J., Huttunen, J., et al. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00893-3 · Cited by 22 · see citing works
Self-citationTHA disrupts mismatch negativity in Alzheimer disease
Riekkinen, P. J., Pääkkönen, A. K., Karhu, J. J. T., et al. (1997) · Psychopharmacology · doi:10.1007/s002130050392 · Cited by 21 · see citing works
Aging and Cholinergic Modulation of the Transient Magnetic 40-Hz Auditory Response
Ahveninen, J., Jääskeläinen, I. P., Kaakkola, S., et al. (2002) · NeuroImage · doi:10.1006/nimg.2001.0956 · Cited by 20 · see citing works
Self-citationIn vivo Probe of Central Cholinergic Systems
Meador, K. J., Loring, D. W., Lee, G. P., et al. (1988) · Journal of Gerontology · doi:10.1093/geronj/43.6.m158 · Cited by 20 · see citing works
Callaway, E., Halliday, R. A., Naylor, H., et al. (1991) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(91)90024-u · Cited by 15 · see citing works
Current Approaches to the Clinical Diagnosis of Alzheimer’s Disease
Daffner, K. R. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-005-6_2 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The mismatch negativity: a review of underlying mechanisms
Garrido, M. I., Kilner, J. M., Stephan, K. E., & Friston, K. J. (2009) · Clinical Neurophysiology · doi:10.1016/j.clinph.2008.11.029 · Cited by 1,441 · see citing works
P50 gating deficit in Alzheimer dementia correlates to frontal neuropsychological function
Thomas, C., vom Berg, I., Rupp, A., Seidl, U., Schröder, J., Roesch-Ely, D., Kreisel, S. H., Mundt, C., & Weisbrod, M. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.05.002 · Cited by 88 · see citing works
Alzheimer's disease and its progression reduce pyramidal cell gain and connectivity
Lanskey, J. H., Jafarian, A., Karadag, M., Kocagoncu, E., Williams, R. S., Yadav, P., Quinn, A. J., Pitt, J., Thayanandan, T., Lowe, S., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70805 · Cited by 2 · see citing works
“For example, mismatch negativity responses are altered by cholinergic antagonists 39 and by deep brain stimulation of the nucleus basalis of Meynert, a major source of cholinergic innervation of the cortex.”
- Authors
- Pekkonen, E., Jääskeläinen, I. P., Kaakkola, S., & Ahveninen, J.
- Affiliations
- University of Helsinki (FI)
- Harvard University (US)
- Corresponding author
- Pekkonen, Eero
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 27
- Issue
- 2
- Pages
- 387-392
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2141091684
- Cited by
- 73
- References
- 35
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 7
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroscience and Music Perception
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
- Keywords
- cholinergic modulation, pre-attentive auditory processing, aging, scopolamine, glycopyrrolate, P50, N1 component, mismatch negativity, P200, auditory event-related potentials, auditory evoked potentials, muscarinic receptors, cholinergic activity, Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Aging, Attention, Auditory Perception, Double-Blind Method, Evoked Potentials, Auditory, Female, Glycopyrrolate, Humans, Functional Laterality, Male, Middle Aged, Neuropsychological Tests, Parasympathetic Nervous System, Parasympatholytics, Scopolamine, Magnetoencephalography
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
