Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus
Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed...
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| description | Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus. |
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Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Lowe, Walton 2015 Lowe, Walton</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c809t-b458f1672db9098d3494c5dc6a02d2beff32ee2c5701cb0eae31eb9f8eb15a553</citedby><cites>FETCH-LOGICAL-c809t-b458f1672db9098d3494c5dc6a02d2beff32ee2c5701cb0eae31eb9f8eb15a553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335042/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335042/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25695496$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lowe, Andrea S</creatorcontrib><creatorcontrib>Walton, Joseph P</creatorcontrib><title>Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.</description><subject>Acoustic noise</subject><subject>Acoustic Stimulation</subject><subject>Acoustics</subject><subject>Amplitudes</subject><subject>Animals</subject><subject>Auditory pathways</subject><subject>Behavior, Animal - drug effects</subject><subject>Bioindicators</subject><subject>Biomarkers</subject><subject>Biomedical engineering</subject><subject>Brain research</subject><subject>Brain stem</subject><subject>Brain Stem - drug effects</subject><subject>Brain Stem - physiopathology</subject><subject>Evoked Potentials, Auditory, Brain Stem - drug effects</subject><subject>Female</subject><subject>Frequency</subject><subject>Hearing loss</subject><subject>Hyperactivity</subject><subject>Information processing</subject><subject>Latency</subject><subject>Liquor</subject><subject>Male</subject><subject>Mice</subject><subject>Neurosciences</subject><subject>Noise</subject><subject>Reflex, Startle - drug effects</subject><subject>Reflex, Startle - physiology</subject><subject>Rodents</subject><subject>Salicylic acid</subject><subject>Sodium</subject><subject>Sodium salicylate</subject><subject>Sodium Salicylate - pharmacology</subject><subject>Sodium Salicylate - therapeutic use</subject><subject>Sodium salicylates</subject><subject>Startle response</subject><subject>Tinnitus</subject><subject>Tinnitus - drug therapy</subject><subject>Tinnitus - physiopathology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPloMo0XwrD4MbCw4NdtSNPTmSxtMiapOP_etNNdprIX0ouGk-d9z8lJTpY9x2iJ6Qq_u3G9t6pd7p2FJcJ4RUj5IDvHgpIFJ4g-PFmfZU9CuEGI0ZLzx9kZYVywQvDzzK3bCF5F42zIjc334M1-lyJtrmyda7BxWGvXDXlsDLlr8riDXPW1ic4f8sorY0OELvcQEhTgfa5yC_3oEYI6jBJjrYl9eJo9alQb4Nn0v8h-fPr4_fLL4ur68-ZyfbXQJRJxURWsbDBfkboSSJQ1LUShWa25QqQmFTQNJQBEsxXCukKggGKoRFNChZlijF5kL4---9YFOfUqSMwZJ0LgkiRicyRqp27k3ptO-YN0ysgx4PxWKh-NbkFyVRWC0FLXwAqMGiE0KIpSOVRQXjbJ68OUra86qKeuzUznO9bs5Nb9lgWlDBVDMW8mA-9-9RCi7EzQ0LbKguvHulcUczrW_eof9P7TTdRWpQMY27iUVw-mcp3yCYYRpola3kOlr4bO6HThjUnxmeDtTJCYCH_iVvUhyM23r__PXv-cs69P2B2oNu6Ca_vxXc7B4ghq70Lw0Nw1GSM5zMVtN-TwXuU0F0n24vSC7kS3g0D_AlyZCds</recordid><startdate>20150219</startdate><enddate>20150219</enddate><creator>Lowe, Andrea S</creator><creator>Walton, Joseph P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150219</creationdate><title>Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus</title><author>Lowe, Andrea S ; Walton, Joseph P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c809t-b458f1672db9098d3494c5dc6a02d2beff32ee2c5701cb0eae31eb9f8eb15a553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Acoustic noise</topic><topic>Acoustic Stimulation</topic><topic>Acoustics</topic><topic>Amplitudes</topic><topic>Animals</topic><topic>Auditory pathways</topic><topic>Behavior, Animal - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lowe, Andrea S</au><au>Walton, Joseph P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-19</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0117228</spage><epage>e0117228</epage><pages>e0117228-e0117228</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25695496</pmid><doi>10.1371/journal.pone.0117228</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acoustic noise Acoustic Stimulation Acoustics Amplitudes Animals Auditory pathways Behavior, Animal - drug effects Bioindicators Biomarkers Biomedical engineering Brain research Brain stem Brain Stem - drug effects Brain Stem - physiopathology Evoked Potentials, Auditory, Brain Stem - drug effects Female Frequency Hearing loss Hyperactivity Information processing Latency Liquor Male Mice Neurosciences Noise Reflex, Startle - drug effects Reflex, Startle - physiology Rodents Salicylic acid Sodium Sodium salicylate Sodium Salicylate - pharmacology Sodium Salicylate - therapeutic use Sodium salicylates Startle response Tinnitus Tinnitus - drug therapy Tinnitus - physiopathology |
| title | Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus |
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