Maximizing negative correlations in resting-state functional connectivity MRI by time-lag
This paper aims to better understand the physiological meaning of negative correlations in resting state functional connectivity MRI (r-fcMRI). The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and w...
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| description | This paper aims to better understand the physiological meaning of negative correlations in resting state functional connectivity MRI (r-fcMRI). The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. Consequently, neuronal regulation of brain circulation may be deduced from the valence of r-fcMRI connectivity. |
| doi_str_mv | 10.1371/journal.pone.0111554 |
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The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. 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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. 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The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. Consequently, neuronal regulation of brain circulation may be deduced from the valence of r-fcMRI connectivity.</description><subject>Adult</subject><subject>Alzheimer's disease</subject><subject>Alzheimers disease</subject><subject>Anatomy</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Biophysics</subject><subject>Blood</subject><subject>Blood volume</subject><subject>Brain</subject><subject>Brain - physiology</subject><subject>Brain circulation</subject><subject>Brain research</subject><subject>Cerebral blood flow</subject><subject>Comparative analysis</subject><subject>Correlation</subject><subject>Cortex</subject><subject>Data analysis</subject><subject>Data processing</subject><subject>Data smoothing</subject><subject>Dopamine</subject><subject>Female</subject><subject>Functional magnetic resonance imaging</subject><subject>Hemodynamics</subject><subject>Homology</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Mathematical analysis</subject><subject>Medicine and Health Sciences</subject><subject>Nerve Net - physiology</subject><subject>Neural networks</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Psychiatry</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research and Analysis Methods</subject><subject>Rest - physiology</subject><subject>Rodents</subject><subject>Spatial smoothing</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Time Factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8tq3DAUhk1padK0b1BaQ6G0C08tybLlTSGEXgYSAukFuhKSfOxRkKWpZA-ZPn01GSeMSxZFC92-80vnl06SvET5ApEKfbh2o7fCLNbOwiJHCFFaPEqOUU1wVuKcPD4YHyXPQrjOc0pYWT5NjjAldVmg8jj5dSFudK__aNulFjox6A2kynkPJo6dDam2qYcwRCALgxggbUerdlvCRNBaiJONHrbpxdUyldt00D1kRnTPkyetMAFeTP1J8uPzp-9nX7Pzyy_Ls9PzTFWUDZmqcQuyJIgKQKIkqikkq5hktJJESlVSjASuKmiQrFXMiLUNlo2qASHAGJOT5PVed21c4JMrgaO6qmtSFQWLxHJPNE5c87XXvfBb7oTmtwvOd1z4QSsDHKK2ytucFHVT5JhJRWRLKwakpSyXRdT6OJ02yh4aBXbwwsxE5ztWr3jnNrzABGNKo8C7ScC732M0lvc6KDBGWHBjvHeJGWN5xCP65h_04ewmqhMxAW1bF89VO1F-WiBGcV2SnUuLB6jYGuh1fEZodVyfBbyfBURmgJuhE2MIfPnt6v_Zy59z9u0BuwJhhlVwZrz9bHOw2IPKuxA8tPcmo5zvKuDODb6rAD5VQAx7dfhA90F3X578BVfvAcE</recordid><startdate>20141114</startdate><enddate>20141114</enddate><creator>Goelman, Gadi</creator><creator>Gordon, Noam</creator><creator>Bonne, Omer</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>20141114</creationdate><title>Maximizing negative correlations in resting-state functional connectivity MRI by time-lag</title><author>Goelman, Gadi ; Gordon, Noam ; Bonne, Omer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-c92feb6315ae1a63cd4b878b857b3bbc6521a277ed1b9c1938fd2bdc9e11e2223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>Anatomy</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Biophysics</topic><topic>Blood</topic><topic>Blood volume</topic><topic>Brain</topic><topic>Brain - 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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>Goelman, Gadi</au><au>Gordon, Noam</au><au>Bonne, Omer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maximizing negative correlations in resting-state functional connectivity MRI by time-lag</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-14</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e111554</spage><epage>e111554</epage><pages>e111554-e111554</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This paper aims to better understand the physiological meaning of negative correlations in resting state functional connectivity MRI (r-fcMRI). The correlations between anatomy-based brain regions of 18 healthy humans were calculated and analyzed with and without a correction for global signal and with and without spatial smoothing. In addition, correlations between anatomy-based brain regions of 18 naïve anesthetized rats were calculated and compared to the human data. T-statistics were used to differentiate between positive and negative connections. The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex. Positive connections were mainly observed between cortical structures while most negative connections were observed between cortical and non-cortical structures with almost no negative connections between non-cortical structures. In both human and rats, negative connections were never observed between bilateral homologous regions. The main difference between positive and negative connections in both the human and rat data was that positive connections became less significant with time-lags, while negative connections became more significant with time-lag. This effect was evident in all four types of analyses (with and without global signal correction and spatial smoothing) but was most significant in the analysis with no correction for the global signal. We hypothesize that the valence of r-fcMRI connectivity reflects the relative contributions of cerebral blood volume (CBV) and flow (CBF) to the BOLD signal and that these relative contributions are location-specific. If cerebral circulation is primarily regulated by CBF in one region and by CBV in another, a functional connection between these regions can manifest as an r-fcMRI negative and time-delayed correlation. Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone. Consequently, neuronal regulation of brain circulation may be deduced from the valence of r-fcMRI connectivity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25396416</pmid><doi>10.1371/journal.pone.0111554</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alzheimer's disease Alzheimers disease Anatomy Animals Biology and Life Sciences Biophysics Blood Blood volume Brain Brain - physiology Brain circulation Brain research Cerebral blood flow Comparative analysis Correlation Cortex Data analysis Data processing Data smoothing Dopamine Female Functional magnetic resonance imaging Hemodynamics Homology Humans Magnetic Resonance Imaging Male Mathematical analysis Medicine and Health Sciences Nerve Net - physiology Neural networks NMR Nuclear magnetic resonance Physiological aspects Physiology Psychiatry Rats Rats, Sprague-Dawley Research and Analysis Methods Rest - physiology Rodents Spatial smoothing Statistical analysis Studies Time Factors |
| title | Maximizing negative correlations in resting-state functional connectivity MRI by time-lag |
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