{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:11Z","timestamp":1772168951998,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.2-182.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000}}],"reference-count":31,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>An auditory oddball paradigm in humans generates a long-duration cortical negative potential, often referred to as mismatch negativity. Similar negativity has been documented in monkeys and cats, but it is controversial whether mismatch negativity also exists in awake rodents. To this end, we recorded cortical and hippocampal evoked responses in rats during alert immobility under a typical passive oddball paradigm that yields mismatch negativity in humans. The standard stimulus was a 9 kHz tone and the deviant either 7 or 11 kHz tone in the first condition. We found no evidence of a sustained potential shift when comparing evoked responses to standard and deviant stimuli. Instead, we found repetition-induced attenuation of the P60 component of the combined evoked response in the cortex, but not in the hippocampus. The attenuation extended over three days of recording and disappeared after 20 intervening days of rest. Reversal of the standard and deviant tones resulted is a robust enhancement of the N40 component not only in the cortex but also in the hippocampus. Responses to standard and deviant stimuli were affected similarly. Finally, we tested the effect of scopolamine in this paradigm. Scopolamine attenuated cortical N40 and P60 as well as hippocampal P60 components, but had no specific effect on the deviant response. We conclude that in an oddball paradigm the rat demonstrates repetition-induced attenuation of mid-latency responses, which resembles attenuation of the N1-component of human auditory evoked potential, but no mismatch negativity.<\/ns4:p>","DOI":"10.12688\/f1000research.2-182.v2","type":"journal-article","created":{"date-parts":[[2014,5,12]],"date-time":"2014-05-12T12:25:22Z","timestamp":1399897522000},"page":"182","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Short- and long-term habituation of auditory event-related potentials in the rat"],"prefix":"10.12688","volume":"2","author":[{"given":"Kestutis","family":"Gurevicius","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arto","family":"Lipponen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rimante","family":"Minkeviciene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heikki","family":"Tanila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"317-37","DOI":"10.3109\/00207459508986107","article-title":"Mismatch negativity--a unique measure of sensory processing in audition.","volume":"80","author":"R Naatanen","year":"1995","journal-title":"Int J Neurosci."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"283-8","DOI":"10.1016\/S0166-2236(00)01790-2","article-title":"\u201cPrimitive intelligence\u201d in the auditory cortex.","volume":"24","author":"M Naatanen","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"38-51","DOI":"10.1097\/00003446-199502000-00004","article-title":"Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes.","volume":"16","author":"K Alho","year":"1995","journal-title":"Ear Hear."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"627-40","DOI":"10.1111\/j.1469-8986.1990.tb03184.x","article-title":"Brain generators implicated in the processing of auditory stimulus deviance: A topographic event-related potential study.","volume":"27","author":"M Giard","year":"1990","journal-title":"Psychophysiology."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"453-63","DOI":"10.1016\/j.clinph.2008.11.029","article-title":"The mismatch negativity: a review of underlying mechanisms.","volume":"120","author":"M Garrido","year":"2009","journal-title":"Clin Neurophysiol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"571-8","DOI":"10.1016\/0013-4694(87)90103-9","article-title":"Evoked potential correlates of stimulus deviance during wakefulness and sleep in cat--animal model of mismatch negativity.","volume":"66","author":"V Csepe","year":"1987","journal-title":"Electroencephalogr Clin Neurophysiol."},{"key":"ref-7","doi-asserted-by":"crossref","first-page":"1270-1277","DOI":"10.1152\/jn.1994.72.3.1270","article-title":"Nonprimary auditory thalamic representation of acoustic change.","volume":"72","author":"N Kraus","year":"1994","journal-title":"J Neurophysiol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"123-6","DOI":"10.1016\/0304-3940(94)11240-J","article-title":"Hippocampal evoked potentials to pitch deviances in an auditory oddball situation in the rabbit: No human mismatch-like dependence on standard stimuli.","volume":"185","author":"T Ruusuvirta","year":"1995","journal-title":"Neurosci Lett."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"87-90","DOI":"10.1016\/0013-4694(92)90137-7","article-title":"Demonstration of mismatch negativity in the monkey.","volume":"83","author":"D Javitt","year":"1992","journal-title":"Electroencephalogr Clin Neurophysiol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"e24208","DOI":"10.1371\/journal.pone.0024208","article-title":"Memory-based mismatch response to frequency changes in rats.","volume":"6","author":"P Astikainen","year":"2011","journal-title":"PLoS One."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"e54624","DOI":"10.1371\/journal.pone.0054624","article-title":"Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats.","volume":"8","author":"T Ruusuvirta","year":"2013","journal-title":"PLoS One."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"279-289","DOI":"10.1007\/978-3-642-74557-7_23","article-title":"Subcortical evoked potential correlates of early information processing: Mismatch negativity in cats. 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\n<i>Posted: 13 Aug 2014<\/i>; Dear Dr. Rosburg&nbsp;\n<i>We would like to thank you for your careful consideration and suggestions to improve our article. Before receiving comments from the other reviewers we would like to exploit the possibility to provide some response before resubmission.<\/i>\n<i>We would like to emphasize that MMN can be found in other species including rat in cortical and hippocampal areas while anaesthetized, but in our study with awake rats, MMN was not detectable. As for other comments we suggest the following corrections.<\/i>1. Figure 2 has now been re-labelled, as showing grand average data from Day 1. At the same time, the graphs are still labelled as \u2018representative examples\u2019. This is not as clear as it should be. First, it is not clear what is meant by \u2018representative\u2019. Second, grand average data should not be called \u2018examples\u2019. Moreover, in Figure 2 the absolute amplitudes of the cortical P60 are larger than the absolute amplitudes of the cortical N40. This is somewhat in contrast to Figure 3 that shows similar absolute amplitudes for the two components. Finally, given the significant difference in the hippocampal P60 between standards and deviants, grand average data of Experiment 2 need to be depicted, as previously requested.&nbsp;\n<i>For clarity we will replace Fig. 2. Title \u201cRepresentative examples of averaged AEPs obtained in the auditory oddball paradigm\u201d by \u201cGroup average of AEPs recorded on the first day of the experiment 1\u201d. We chose these data because it is the first day of the exposure to auditory stimuli, and as such represents the shape of the waveform of other recordings, too. <\/i>&nbsp;\n<i>Figure 2 represents the group average for the raw data while Fig. 3 shows the average of maximum peak amplitudes within these time windows. Since the components had some latency variation (see Table 1), the two ways of averaging the responses do not necessary lead to the same result. <\/i>&nbsp;\n<i>Because of the huge amount of raw data and the format of the journal, we are, unfortunately, not able to provide all the complimentary figures of all our significant findings.However, as we strongly support transparency of scientific data and discussion, we would be pleased to provide additional figures for any interested reader. <\/i>2. The authors do not describe how artefacts were identified and on what basis data were excluded. It is insufficient to state that data were excluded due to a \u201cpoor signal (i.e. bad electrode contact)\u201d. Such a description hinders any replication of the study.\n<i>We will add the following sentence to our resubmission \u201cTypical excluded signal had a large number of discontinuities, signal was saturated or line frequency (50 Hz) pick-up exceeds 100 uV. Signal saturation indicates electrode detachment, large discontinuities indicate loose contacts, excessive noise indicates problem with electrode.\u201d<\/i>3. It is still not fully clear what reference electrode was used. The authors state a \u201ccommon reference electrode\u201d was used but they do not describe which electrodes were used for calculating it.\n<i>In the methods section we described the following \u201cA frontal screw was selected as the ground and a common reference electrode\u2026\u201d. This recording methodology is the traditional method in rodent electrophysiology but different from human EEG recording methodology.<\/i>4. As also previously criticized by other reviewers, the description of the conducted statistics is incomplete with some F values missing, but there are some inconsistencies as well.&nbsp;\n<i>We will add the missing F values whenever there is a significant p-value. <\/i>&nbsp;(a), Table 1 implies that one data point each was excluded from the analysis of Experiment 1. However, the submitted data file does not contain missing values. Consequently, the data file is hardly suited to reproduce the study results.&nbsp;\n<i>We have provided data collected from three experiments and the missing values are marked as n.a. This implies that data were excluded because of recording artefacts, as previously stated, or data were not available in this experiment.<\/i>&nbsp;(b), it is also worth noting that the algebraic signs are reversed in this data file (with positive values for the N40 and negative for the P60 and P110 amplitude values).\n<i>We thank for this careful notice.<\/i>(c), furthermore, attempts to reproduce the study results are hampered by the fact that sometimes the degrees of freedom are incorrectly reported (in particular for the repetition effects). Moreover, for the repetition effects, it is unclear whether the reported results of the ANOVA were Greenhouse-Geisser corrected when necessary. This needs to be indicated. - When I re-calculated the repetition effect of the cortical P60 in an ANOVA with Day (Day 1 vs. Day 2 vs. Day 3) and ODDBALL (standards vs. deviants) as within-subjects factors with the provided data, I revealed an insignificant main effect of DAY [F (2, 16) = 3.451, p = 0.094 after Greenhouse-Geisser correction, epsilon = 0.556].\n<i>The reported results were tested by General Linear Model, Repeated Measures with two Independent Variables (Day =3 levels, Sound=2 levels). If data violate the sphericity assumption there are several corrections that can be applied to produce a valid F-ratio (Greenhouse\u2013Geisser correction is one of them). Other option is to use multivariate test, because it is not dependent upon the assumption of sphericity and SPSS will automatically produce test statistics. In case of cortical P60 during Experiment 1, we could find, for example, Pillai\u2019s trace Value=0.066, F(2,6)=5,87; P=0.039 [IBM SPSS Statistics Version 21]. This is exactly what is reported in the article.<\/i>&nbsp;5. As previously mentioned, the concepts of \u2018long-term habituation\u2019, \u2018short-term habituation\u2019 and \u2018long-term adaptation\u2019 are poorly described and no explicit operational definitions are provided. On the basis of previous 'long-term habituation' studies in humans, I would not expect to see response decrements from day to day but within each experimental day (i.e. within an experimental session); on the basis of the provided data, I am little convinced that there were actually any substantial response decrements from day to day in Experiment 1 (see comment point 4 c).\n<i>Short-term refers changes observed during a single odd-ball trial while long-term changes take place over days.&nbsp; We will clarify our terminology and provide additional information of the temporal scale of short- and long-term adaption in our resubmission. <\/i>\n<i>For further comments, see previous response. <\/i>&nbsp;6. The authors argue that the contrast between the present and previous studies \u201ccan be ascribed to the confounding effect of anesthesia on neuronal functions, as evidenced in a human anesthesia study\u201d. This is not particularly convincing since the cited study of Heinke et al. (2004) showed that the human MMN is diminished by anesthesia rather than the other way around. Moreover, the authors claim in the Introduction that the &quot;severity of Alzheimer\u2019s disease, and presumable the progression of hippocampal damage, is related to the MMN amplitude decrement&quot;, referring to the study of). However, the severity of Alzheimer\u2019s disease and the progression of hippocampal damage were not related to the MMN amplitude decrement in this study.\n<i>We have rephrased this sentence (\u201ccan be ascribed to the confounding effect of anesthesia on consciousness level\u201d) to the following for clarity. In rodents, high doses of the standard anesthesia, urethane, severely reduces MMN amplitude (our unpublished finding). Notably, a light anesthesia in rats enables to elicit MMN which is not seen in awake state. Therefore, it seems that rats need to be lightly sedated to a produce state similar to human pre-attentive state.<\/i>\n<i>Previous version of the sentence \u201cSeverity of Alzheimer\u2019s disease, and presumable the progression of hippocampal damage, is related to the MMN amplitude decrement&quot;, will be replaced in the resubmission \u201cAs it has been noted, that Alzheimer\u2019s disease affects MMN. When MMN amplitude was measured as a function of the inter-stimulus-interval the Alzheimer\u2019s disease patients showed more decrease as age-matched controls<\/i> \n<i>Pekkonen et al. (1994).\u201d <\/i>&nbsp;7. The authors need to clarify to what data the correlation matrix in Table 2 refers to, as previously noted.\n<i>As described in the text, Table 2 summarizes mutual correlations between amplitudes of middle-latency components. The mutual Pearson correlation coefficients were high and significant for all components of the hippocampal response (if the absolute value of one component grows there is a high probability that other components will also grow).<\/i>&nbsp;8. The title of the study needs to be re-considered, as previously outlined.\n<i>See, answer to part 5. <\/i>","URL":"https:\/\/f1000research.com\/articles\/2-182\/v2#referee-comment-940","order":2,"name":"referee-comment-940","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.2055.r2955, Colin Lever, Department of Psychology, Durham University, Durham, UK, 10 Mar 2014, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/2-182\/v1#referee-response-2955","order":3,"name":"referee-response-2955","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}