Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability

  1. Ian A Clark
  2. Siawoosh Mohammadi
  3. Martina F Callaghan
  4. Eleanor A Maguire  Is a corresponding author
  1. Wellcome Centre for Human Neuroimaging, Department of Imaging Neuroscience, UCL Queen Square Institute of Neurology, University College London, United Kingdom
  2. Institute of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Germany
16 figures, 22 tables and 3 additional files

Figures

Schematic of a myelinated axon showing how the g-ratio is calculated.
Illustration of how the MR g-ratio relates to specific microstructural properties given a faster conduction velocity.

(A) Graphical representation of the relationships between myelin thickness, inner axon diameter and MR g-ratio, assuming a faster conduction velocity (see Appendix 1 for details of the simulation). Myelin thickness is represented by the gradient in background colour and contours on the graph, with the thinnest myelin at the bottom right and thickest at the top left. The direction of the arrows describes the change in g-ratio for each microstructural variation presented in B-E. The positioning and colours of the arrows correspond to the text box outline colours in B-E. (B–E) Illustrations of how changes in the MR g-ratio relate to the underlying axonal microstructure, given a faster conduction velocity.

The three white matter tracts of interest, given their relationship with the hippocampal region.

The fornix was defined using the ICBM-DTI-81 white-matter labels atlas (Mori et al., 2008). The uncinate fasciculus and parahippocampal cingulum bundle were defined using the Johns Hopkins probabilistic white matter tractography atlas (Hua et al., 2008), with the minimum probability threshold set to 25%.

Simplified schematic of the location and main connections of the parahippocampal cingulum bundle.

The blue lines indicate direct connections, and the dashed blue line an indirect connection.

MR g-ratio and the parahippocampal cingulum bundle.

The relationship between parahippocampal cingulum bundle MR g-ratio and autobiographical memory recall ability (internal details), and the control measure (external details) are shown. (A) There was a significant positive correlation between the MR g-ratio and internal details (dashed lines indicate the confidence intervals). (B) There was no significant relationship between the MR g-ratio and external details. (C) Bar chart showing the partial correlation coefficients (with standard errors) between the MR g-ratio and internal and external details. There was a significant difference between the correlations when they were directly compared; ***p<0.001. Data points for this figure are provided in Figure 5—source data 1, n = 217 for all analyses.

Neurite dispersion and the parahippocampal cingulum bundle.

The relationship between parahippocampal cingulum bundle neurite dispersion (orientation dispersion index) and autobiographical memory recall ability (internal details), and the control measure (external details) are shown. (A) There was a significant negative correlation between neurite dispersion and internal details (dashed lines indicate the confidence intervals). (B) There was no significant relationship between neurite dispersion and external details. (C) Bar chart showing the partial correlation coefficients (with standard errors) between neurite dispersion and internal and external details. There was a significant difference between the correlations when they were directly compared; **p<0.01. Data points for this figure are provided in the Figure 6—source data 1, n = 217 for all analyses.

Appendix 1—figure 1
The location of the fornix.
Appendix 1—figure 2
The location of the uncinate fasciculus.
Appendix 1—figure 3
The location of the anterior thalamic radiation.
Appendix 1—figure 4
The location of the dorsal cingulum bundle.
Appendix 1—figure 5
The location of the forceps minor.
Appendix 1—figure 6
The location of the inferior longitudinal fasciculus.
Appendix 1—figure 7
The location of the inferior occipitofrontal fasciculus.
Appendix 1—figure 8
The location of the superior longitudinal fasciculus.
Appendix 1—figure 9
Fractional anisotropy (FA) and the parahippocampal cingulum bundle.

The relationships between parahippocampal cingulum bundle FA and autobiographical memory recall ability (internal details), and the control measure (external details) are shown. (A) There was a significant positive correlation between FA and internal details (dashed lines indicate the confidence intervals). (B) There was no significant relationship between FA and external details. (C) Bar chart showing the partial correlation coefficients (with standard errors) between FA and internal and external details. There was a significant difference between the correlations when they were directly compared; **p<0.01. Data points for this figure are provided in Supplementary file 2.

Appendix 1—figure 10
Dpara and the parahippocampal cingulum bundle.

The relationships between parahippocampal cingulum bundle diffusivities parallel (Dpara) and autobiographical memory recall ability (internal details), and the control measure (external details) are shown. (A) There was a significant positive correlation between Dpara and internal details (dashed lines indicate the confidence intervals). (B) There was no significant relationship between Dpara and external details. (C) Bar chart showing the partial correlation coefficients (with standard errors) between Dpara and internal and external details. There was a significant difference between the correlations when they were directly compared; **p<0.01. Data points for this figure are provided in Supplementary file 2.

Tables

Table 1
Means and standard deviations for the microstructure measures from the parahippocampal cingulum bundle.
Microstructure measureMeanStandard deviation
MR g-ratio0.6470.043
Magnetisation transfer saturation0.9590.007
Neurite dispersion (ODI)0.1890.038
Neurite density0.4800.051
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 1
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the fornix.
MeasureMeanStandard deviation
MR g-ratio0.7200.017
Magnetisation transfer saturation0.9730.003
Neurite dispersion (ODI)0.1430.021
Neurite density0.6010.045
Fractional anisotropy0.6050.035
Mean diffusivity (10–3 mm2/s)0.9010.036
Mean kurtosis0.9090.100
Diffusivities parallel (10–3 mm2/s)1.6450.072
Diffusivities perpendicular (10–3 mm2/s)0.5290.042
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 2
Partial correlations between the microstructure measures or standard DTI parameters extracted from the fornix and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio–0.040.53–0.160.08
Magnetisation transfer saturation–0.080.23–0.200.03
Neurite dispersion (ODI)–0.030.62–0.160.10
Neurite density–0.030.69–0.150.10
Fractional anisotropy0.020.80–0.120.15
Mean diffusivity0.070.35–0.080.21
Mean kurtosis–0.030.66–0.160.10
Diffusivities parallel0.050.46–0.090.19
Diffusivities perpendicular0.020.74–0.120.15
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 3
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the uncinate fasciculus.
MeasureMeanStandard deviation
MR g-ratio0.7230.016
Magnetisation transfer saturation0.9720.003
Neurite dispersion (ODI)0.1890.022
Neurite density0.5620.045
Fractional anisotropy0.5120.036
Mean diffusivity (10–3 mm2/s)0.8770.304
Mean kurtosis0.9130.100
Diffusivities parallel (10–3 mm2/s)1.4560.055
Diffusivities perpendicular (10–3 mm2/s)0.5880.039
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 4
Partial correlations between the microstructure measures or standard DTI parameters extracted from the uncinate fasciculus and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.100.15–0.030.22
Magnetisation transfer saturation–0.020.81–0.140.11
Neurite dispersion (ODI)–0.010.94–0.140.13
Neurite density0.010.89–0.140.16
Fractional anisotropy–0.010.94–0.140.13
Mean diffusivity–0.010.87–0.140.13
Mean kurtosis–0.010.91–0.130.18
Diffusivities parallel–0.010.87–0.140.13
Diffusivities perpendicular0.000.96–0.150.14
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 5
Partial correlations between the fornix MR g-ratio and magnetisation transfer saturation values and the laboratory-based memory tests.
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio
Logical Memory immediate recall–0.010.85–0.140.11
Logical Memory delayed recall–0.070.33–0.190.06
RAVLT immediate recall–0.060.42–0.200.09
RAVLT delayed recall0.000.98–0.140.15
Rey-Osterrieth Complex Figure delayed recall0.100.16–0.040.23
Warrington RMT for Words0.040.59–0.080.16
Warrington RMT for Faces–0.050.52–0.170.09
Dead or Alive Test–0.050.50–0.160.09
Magnetisation transfer saturation
Logical Memory immediate recall0.040.53–0.110.19
Logical Memory delayed recall0.110.11–0.040.26
RAVLT immediate recall0.010.92–0.110.13
RAVLT delayed recall0.030.71–0.090.15
Rey-Osterrieth Complex Figure delayed recall0.070.33–0.060.19
Warrington RMT for Words0.060.41–0.050.17
Warrington RMT for Faces0.040.61–0.090.16
Dead or Alive Test0.080.25–0.060.21
  1. Note. RAVLT = Rey Auditory Verbal Learning Test; RMT = Recognition Memory Test.

Appendix 1—table 6
Partial correlations between the uncinate fasciculus MR g-ratio and magnetisation transfer saturation values and the laboratory-based memory tests.
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio
Logical Memory immediate recall0.070.34–0.060.19
Logical Memory delayed recall0.040.34–0.090.17
RAVLT immediate recall0.000.98–0.140.13
RAVLT delayed recall0.060.40–0.100.21
Rey-Osterrieth Complex Figure delayed recall0.010.94–0.130.15
Warrington RMT for Words–0.010.86–0.160.15
Warrington RMT for Faces–0.070.34–0.200.06
Dead or Alive Test–0.040.60–0.150.08
Magnetisation transfer saturation
Logical Memory immediate recall–0.040.53–0.170.09
Logical Memory delayed recall–0.050.49–0.180.09
RAVLT immediate recall–0.130.06–0.260.01
RAVLT delayed recall–0.160.02–0.27–0.03
Rey-Osterrieth Complex Figure delayed recall–0.070.33–0.200.07
Warrington RMT for Words–0.140.04–0.26–0.01
Warrington RMT for Faces–0.050.44–0.180.09
Dead or Alive Test–0.010.93–0.140.13
  1. Note. RAVLT = Rey Auditory Verbal Learning Test; RMT = Recognition Memory Test.

Appendix 1—table 7
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the anterior thalamic radiation.
MeasureMeanStandard deviation
MR g-ratio0.7240.014
Magnetisation transfer saturation0.9860.001
Neurite dispersion (ODI)0.2520.017
Neurite density0.5980.041
Fractional anisotropy0.4300.028
Mean diffusivity (10–3 mm2/s)0.8610.029
Mean kurtosis0.9860.063
Diffusivities parallel (10–3 mm2/s)1.3280.041
Diffusivities perpendicular (10–3 mm2/s)0.6270.034
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 8
Partial correlations between the microstructure measures or standard DTI parameters extracted from the anterior thalamic radiation and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.050.47–0.060.17
MT sat–0.080.26–0.200.04
Neurite dispersion (ODI)–0.050.46–0.180.09
Neurite density0.100.16–0.040.23
Fractional anisotropy0.080.26–0.060.21
Mean diffusivity0.030.67–0.110.17
Mean kurtosis0.070.28–0.070.22
Diffusivities parallel0.090.20–0.040.21
Diffusivities perpendicular–0.020.77–0.160.12
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 9
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the dorsal cingulum bundle.
MeasureMeanStandard deviation
MR g-ratio0.7100.016
Magnetisation transfer saturation0.9840.003
Neurite dispersion (ODI)0.1470.019
Neurite density0.5600.038
Fractional anisotropy0.5700.039
Mean diffusivity (10–3 mm2/s)0.8620.026
Mean kurtosis0.8620.093
Diffusivities parallel (10–3 mm2/s)1.5310.061
Diffusivities perpendicular (10–3 mm2/s)0.5270.040
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 10
Partial correlations between the microstructure measures or standard DTI parameters extracted from the dorsal cingulum bundle and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.090.22–0.040.21
MT sat0.080.23–0.040.21
Neurite dispersion (ODI)0.090.17–0.050.23
Neurite density0.090.17–0.050.23
Fractional anisotropy0.010.85–0.130.16
Mean diffusivity0.060.43–0.080.19
Mean kurtosis0.130.050.000.27
Diffusivities parallel0.050.48–0.080.18
Diffusivities perpendicular0.010.91–0.140.15
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 11
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the forceps minor.
MeasureMeanStandard deviation
MR g-ratio0.6980.026
Magnetisation transfer saturation0.9930.002
Neurite dispersion (ODI)0.2010.016
Neurite density0.6010.042
Fractional anisotropy0.5000.027
Mean diffusivity (10–3 mm2/s)0.8810.031
Mean kurtosis0.9470.128
Diffusivities parallel (10–3 mm2/s)1.4670.052
Diffusivities perpendicular (10–3 mm2/s)0.5880.034
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 12
Partial correlations between the microstructure measures or standard DTI parameters extracted from the forceps minor and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.040.53–0.070.18
MT sat0.070.34–0.060.19
Neurite dispersion (ODI)–0.060.38–0.210.07
Neurite density0.090.19–0.040.22
Fractional anisotropy0.100.17–0.030.23
Mean diffusivity–0.040.56–0.170.09
Mean kurtosis0.000.97–0.110.21
Diffusivities parallel0.030.67–0.090.18
Diffusivities perpendicular–0.070.32–0.190.05
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 13
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the inferior longitudinal fasciculus.
MeasureMeanStandard deviation
MR g-ratio0.7240.013
Magnetisation transfer saturation0.9940.002
Neurite dispersion (ODI)0.1840.017
Neurite density0.5580.041
Fractional anisotropy0.4860.028
Mean diffusivity (10–3 mm2/s)0.9020.029
Mean kurtosis0.9180.061
Diffusivities parallel (10–3 mm2/s)1.4730.045
Diffusivities perpendicular (10–3 mm2/s)0.6160.035
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 14
Partial correlations between the microstructure measures or standard DTI parameters extracted from the inferior longitudinal fasciculus and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.070.35–0.060.19
MT sat0.070.35–0.050.18
Neurite dispersion (ODI)–0.030.64–0.170.10
Neurite density0.070.35–0.070.19
Fractional anisotropy0.100.14–0.040.23
Mean diffusivity–0.010.87–0.150.13
Mean kurtosis0.100.16–0.030.23
Diffusivities parallel0.070.29–0.070.21
Diffusivities perpendicular–0.070.34–0.190.07
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 15
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the inferior occipitofrontal fasciculus.
MeasureMeanStandard deviation
MR g-ratio0.7290.011
Magnetisation transfer saturation0.9950.001
Neurite dispersion (ODI)0.1790.012
Neurite density0.5630.036
Fractional anisotropy0.5080.024
Mean diffusivity (10–3 mm2/s)0.8890.026
Mean kurtosis0.9120.057
Diffusivities parallel (10–3 mm2/s)1.4880.039
Diffusivities perpendicular (10–3 mm2/s)0.5900.031
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 16
Partial correlations between the microstructure measures or standard DTI parameters extracted from the inferior occipitofrontal fasciculus and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio–0.010.93–0.120.12
MT sat0.080.22–0.030.19
Neurite dispersion (ODI)–0.010.89–0.140.13
Neurite density0.060.42–0.070.18
Fractional anisotropy0.060.38–0.080.20
Mean diffusivity0.000.99–0.130.13
Mean kurtosis0.070.31–0.060.19
Diffusivities parallel0.050.50–0.090.18
Diffusivities perpendicular–0.030.62–0.170.10
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 17
Means and standard deviations for the microstructure measures and standard DTI parameters extracted from the superior longitudinal fasciculus.
MeasureMeanStandard deviation
MR g-ratio0.7510.011
Magnetisation transfer saturation0.9960.001
Neurite dispersion (ODI)0.2180.012
Neurite density0.6340.034
Fractional anisotropy0.4710.026
Mean diffusivity (10–3 mm2/s)0.8250.025
Mean kurtosis1.0290.041
Diffusivities parallel (10–3 mm2/s)1.3240.035
Diffusivities perpendicular (10–3 mm2/s)0.5750.041
  1. Note. ODI = Orientation Dispersion Index.

Appendix 1—table 18
Partial correlations between microstructure measures or standard DTI parameters extracted from the superior longitudinal fasciculus and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio0.080.28–0.050.20
MT sat–0.040.54–0.160.08
Neurite dispersion (ODI)–0.090.17–0.230.05
Neurite density0.120.09–0.010.24
Fractional anisotropy0.130.050.010.26
Mean diffusivity–0.020.80–0.140.11
Mean kurtosis0.110.12–0.030.24
Diffusivities parallel0.120.09–0.030.25
Diffusivities perpendicular–0.080.23–0.200.03
  1. Note. MT sat = Magnetisation Transfer saturation; ODI = Orientation Dispersion Index.

Appendix 1—table 19
Means and standard deviations for the standard DTI parameters extracted from the parahippocampal cingulum bundle.
MeasureMeanStandard deviation
Fractional anisotropy0.4660.053
Mean diffusivity (10–3 mm2/s)0.9310.041
Mean kurtosis0.7790.122
Diffusivities parallel (10–3 mm2/s)1.4790.071
Diffusivities perpendicular (10–3 mm2/s)0.6560.057
Appendix 1—table 20
Partial correlations between the standard DTI parameters extracted from the parahippocampal cingulum bundle and autobiographical memory recall ability (internal details).
Measurer(211)p95% Confidence interval
LowerUpper
Fractional anisotropy0.200.003*0.070.32
Mean diffusivity–0.020.72–0.150.11
Mean kurtosis0.080.23–0.050.21
Diffusivities parallel0.190.005*0.060.32
Diffusivities perpendicular0.150.03–0.27–0.02
  1. *

    p < 0.017 (two-sided Bonferroni corrected threshold).

Appendix 1—table 21
Partial correlations between the parahippocampal cingulum bundle MR g-ratio and magnetisation transfer saturation values and the laboratory-based memory tests.
Measurer(211)p95% Confidence interval
LowerUpper
MR g-ratio
Logical Memory immediate recall0.010.93–0.130.13
Logical Memory delayed recall–0.050.46–0.180.08
RAVLT immediate recall–0.060.41–0.180.07
RAVLT delayed recall–0.090.17–0.210.04
Rey-Osterrieth Complex Figure delayed recall0.070.34–0.060.19
Warrington RMT for Words0.020.80–0.110.16
Warrington RMT for Faces–0.040.53–0.170.10
Dead or Alive Test0.020.79–0.110.15
Magnetisation transfer saturation
Logical Memory immediate recall0.070.35–0.060.19
Logical Memory delayed recall0.010.91–0.120.14
RAVLT immediate recall–0.010.90–0.140.14
RAVLT delayed recall–0.020.80–0.140.11
Rey-Osterrieth Complex Figure delayed recall–0.090.21–0.230.05
Warrington RMT for Words–0.090.21–0.220.04
Warrington RMT for Faces–0.050.49–0.170.09
Dead or Alive Test0.110.11–0.010.23
  1. Note. RAVLT = Rey Auditory Verbal Learning Test; RMT = Recognition Memory Test.

Additional files

Supplementary file 1

Microstructure and standard DTI parameters data for the fornix and uncinate fasciculus.

https://cdn.elifesciences.org/articles/79303/elife-79303-supp1-v1.xlsx
Supplementary file 2

Microstructure and standard DTI parameters data for the parahippocampal cingulum bundle and source data for Appendix 1—figures 9 and 10.

https://cdn.elifesciences.org/articles/79303/elife-79303-supp2-v1.xlsx
MDAR checklist
https://cdn.elifesciences.org/articles/79303/elife-79303-mdarchecklist1-v1.docx

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  1. Ian A Clark
  2. Siawoosh Mohammadi
  3. Martina F Callaghan
  4. Eleanor A Maguire
(2022)
Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability
eLife 11:e79303.
https://doi.org/10.7554/eLife.79303