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Maximizing negative correlations in resting-state functional connectivity MRI by time-lag.

Goelman G, Gordon N, Bonne O - PLoS ONE (2014)

Bottom Line: The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex.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.Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone.

View Article: PubMed Central - PubMed

Affiliation: MRI/MRS Lab, The Human Biology Research Center, Department of Medical Biophysics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

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.

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Categorization of positive and negative human connections.Percentages of significant connections into the ‘Intra Cx’ (between two cortical ROIs), the ‘Extra-Cx’ (between two non-cortical ROIs) and the ‘Between’ (between cortical and non-cortical ROIs) categories. Top. Positive connections. Bottom. Negative connections.
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pone-0111554-g007: Categorization of positive and negative human connections.Percentages of significant connections into the ‘Intra Cx’ (between two cortical ROIs), the ‘Extra-Cx’ (between two non-cortical ROIs) and the ‘Between’ (between cortical and non-cortical ROIs) categories. Top. Positive connections. Bottom. Negative connections.

Mentions: Careful inspection of Figures 2–5 suggests that negative and positive connections differ with respect to the structures they connect. To quantify this point, we categorized all negative and positive significant connections into three types: those connecting between two cortical ROIs ("Intra-Cx"), those connecting between two non-cortical ROIs ("Extra-Cx"), and those connecting a cortical with a non-cortical ROI ("Between"). The percentages of these categories are shown in Figure 7 for the four different analyses of the human data. There was a clear distinction between positive and negative connections with almost no negative connections linking non-cortical regions and only few positive connections linking cortical and non-cortical regions. As seen in Figure 7, the effect of the different analyses on the distribution of positive connections was small while it was greater on the negative connections. Spatial smoothing had a relatively minor effect compared to the significant effect of global regression.


Maximizing negative correlations in resting-state functional connectivity MRI by time-lag.

Goelman G, Gordon N, Bonne O - PLoS ONE (2014)

Categorization of positive and negative human connections.Percentages of significant connections into the ‘Intra Cx’ (between two cortical ROIs), the ‘Extra-Cx’ (between two non-cortical ROIs) and the ‘Between’ (between cortical and non-cortical ROIs) categories. Top. Positive connections. Bottom. Negative connections.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232255&req=5

pone-0111554-g007: Categorization of positive and negative human connections.Percentages of significant connections into the ‘Intra Cx’ (between two cortical ROIs), the ‘Extra-Cx’ (between two non-cortical ROIs) and the ‘Between’ (between cortical and non-cortical ROIs) categories. Top. Positive connections. Bottom. Negative connections.
Mentions: Careful inspection of Figures 2–5 suggests that negative and positive connections differ with respect to the structures they connect. To quantify this point, we categorized all negative and positive significant connections into three types: those connecting between two cortical ROIs ("Intra-Cx"), those connecting between two non-cortical ROIs ("Extra-Cx"), and those connecting a cortical with a non-cortical ROI ("Between"). The percentages of these categories are shown in Figure 7 for the four different analyses of the human data. There was a clear distinction between positive and negative connections with almost no negative connections linking non-cortical regions and only few positive connections linking cortical and non-cortical regions. As seen in Figure 7, the effect of the different analyses on the distribution of positive connections was small while it was greater on the negative connections. Spatial smoothing had a relatively minor effect compared to the significant effect of global regression.

Bottom Line: The application of spatial smoothing and global signal correction increased the number of significant positive connections but their effect on negative connections was complex.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.Similarly, negative correlations could result from spatially inhomogeneous responses of rCBV or rCBF alone.

View Article: PubMed Central - PubMed

Affiliation: MRI/MRS Lab, The Human Biology Research Center, Department of Medical Biophysics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

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.

Show MeSH