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Marked effects of intracranial volume correction methods on sex differences in neuroanatomical structures: a HUNT MRI study.

Pintzka CW, Hansen TI, Evensmoen HR, Håberg AK - Front Neurosci (2015)

Bottom Line: Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small.The residuals and ANCOVA methods were most effective at removing the effects of ICV.Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Norwegian University of Science and Technology Trondheim, Norway ; Department of Medical Imaging, St. Olav's University Hospital Trondheim, Norway.

ABSTRACT
To date, there is no consensus whether sexual dimorphism in the size of neuroanatomical structures exists, or if such differences are caused by choice of intracranial volume (ICV) correction method. When investigating volume differences in neuroanatomical structures, corrections for variation in ICV are used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as a covariate of no interest, ANCOVA. However, these different methods give contradictory results with regard to presence of sex differences. Our aims were to investigate presence of sexual dimorphism in 18 neuroanatomical volumes unrelated to ICV-differences by using a large ICV-matched subsample of 304 men and women from the HUNT-MRI general population study, and further to demonstrate in the entire sample of 966 healthy subjects, which of the ICV-correction methods gave results similar to the ICV-matched subsample. In addition, sex-specific subsamples were created to investigate whether differences were an effect of head size or sex. Most sex differences were related to volume scaling with ICV, independent of sex. Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small. The residuals and ANCOVA methods were most effective at removing the effects of ICV. The proportions method suffered from systematic errors due to lack of proportionality between ICV and neuroanatomical volumes, leading to systematic mis-assignment of structures as either larger or smaller than their actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method. The findings in the current study explain some of the considerable variation in the literature on sexual dimorphisms in neuroanatomical volumes. In conclusion, sex plays a minor role for neuroanatomical volume differences; most differences are related to ICV.

No MeSH data available.


Related in: MedlinePlus

Differences between the large vs. small ICV-groups in the men- and women-only subsamples. The bars illustrate mean standardized volume for the large-ICV groups (blue) and small-ICV groups (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-corrected using the residuals method on the male subsample. Top right: ICV-corrected using the proportions method on the male subsample. Bottom left: ICV-corrected using the residuals method on the female subsample. Bottom right: ICV-corrected using the proportions method on the female subsample. *Corrected p < 0.05.
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Figure 7: Differences between the large vs. small ICV-groups in the men- and women-only subsamples. The bars illustrate mean standardized volume for the large-ICV groups (blue) and small-ICV groups (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-corrected using the residuals method on the male subsample. Top right: ICV-corrected using the proportions method on the male subsample. Bottom left: ICV-corrected using the residuals method on the female subsample. Bottom right: ICV-corrected using the proportions method on the female subsample. *Corrected p < 0.05.

Mentions: The subsamples consisted of 450 (men) and 516 (women) subjects, respectively. There were no differences in age between the large- and small-ICV groups in the male (59.1 ± 4.0 vs. 58.4 ± 4.2 years; p = 0.116) or female (58.2 ± 4.2 vs. 58.2 ± 4.4 years; p = 0.882) subsample. Each of the four groups had normally distributed ICVs, and mean ICV was significantly larger in the large-ICV group in the male (1758.6 ± 77.7 vs. 1578.2 ± 88.7 ml; p < 0.001) and female (1529.4 ± 77.1 vs. 1380.2 ± 93.0 ml; p < 0.001) subsample (Figure 2). Using the residuals method, no structures were significantly different between the small and large ICV groups for either sex. When using the proportions method to correct for ICV in the men-only subsample, the large-ICV group was found to have larger cerebral white matter and lateral ventricle (both with a negative y-intercept, group B), whereas the small-ICV group had larger accumbens, amygdala, caudate, cerebellar, and cerebral cortex, hippocampus, pallidum, putamen, and thalamus (all with a positive y-intercept, group A). Using the proportions method on the women-only subsample gave identical results. In addition, the small-ICV women group had significantly larger brainstem (group A) (Figure 7).


Marked effects of intracranial volume correction methods on sex differences in neuroanatomical structures: a HUNT MRI study.

Pintzka CW, Hansen TI, Evensmoen HR, Håberg AK - Front Neurosci (2015)

Differences between the large vs. small ICV-groups in the men- and women-only subsamples. The bars illustrate mean standardized volume for the large-ICV groups (blue) and small-ICV groups (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-corrected using the residuals method on the male subsample. Top right: ICV-corrected using the proportions method on the male subsample. Bottom left: ICV-corrected using the residuals method on the female subsample. Bottom right: ICV-corrected using the proportions method on the female subsample. *Corrected p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4496575&req=5

Figure 7: Differences between the large vs. small ICV-groups in the men- and women-only subsamples. The bars illustrate mean standardized volume for the large-ICV groups (blue) and small-ICV groups (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-corrected using the residuals method on the male subsample. Top right: ICV-corrected using the proportions method on the male subsample. Bottom left: ICV-corrected using the residuals method on the female subsample. Bottom right: ICV-corrected using the proportions method on the female subsample. *Corrected p < 0.05.
Mentions: The subsamples consisted of 450 (men) and 516 (women) subjects, respectively. There were no differences in age between the large- and small-ICV groups in the male (59.1 ± 4.0 vs. 58.4 ± 4.2 years; p = 0.116) or female (58.2 ± 4.2 vs. 58.2 ± 4.4 years; p = 0.882) subsample. Each of the four groups had normally distributed ICVs, and mean ICV was significantly larger in the large-ICV group in the male (1758.6 ± 77.7 vs. 1578.2 ± 88.7 ml; p < 0.001) and female (1529.4 ± 77.1 vs. 1380.2 ± 93.0 ml; p < 0.001) subsample (Figure 2). Using the residuals method, no structures were significantly different between the small and large ICV groups for either sex. When using the proportions method to correct for ICV in the men-only subsample, the large-ICV group was found to have larger cerebral white matter and lateral ventricle (both with a negative y-intercept, group B), whereas the small-ICV group had larger accumbens, amygdala, caudate, cerebellar, and cerebral cortex, hippocampus, pallidum, putamen, and thalamus (all with a positive y-intercept, group A). Using the proportions method on the women-only subsample gave identical results. In addition, the small-ICV women group had significantly larger brainstem (group A) (Figure 7).

Bottom Line: Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small.The residuals and ANCOVA methods were most effective at removing the effects of ICV.Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Norwegian University of Science and Technology Trondheim, Norway ; Department of Medical Imaging, St. Olav's University Hospital Trondheim, Norway.

ABSTRACT
To date, there is no consensus whether sexual dimorphism in the size of neuroanatomical structures exists, or if such differences are caused by choice of intracranial volume (ICV) correction method. When investigating volume differences in neuroanatomical structures, corrections for variation in ICV are used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as a covariate of no interest, ANCOVA. However, these different methods give contradictory results with regard to presence of sex differences. Our aims were to investigate presence of sexual dimorphism in 18 neuroanatomical volumes unrelated to ICV-differences by using a large ICV-matched subsample of 304 men and women from the HUNT-MRI general population study, and further to demonstrate in the entire sample of 966 healthy subjects, which of the ICV-correction methods gave results similar to the ICV-matched subsample. In addition, sex-specific subsamples were created to investigate whether differences were an effect of head size or sex. Most sex differences were related to volume scaling with ICV, independent of sex. Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small. The residuals and ANCOVA methods were most effective at removing the effects of ICV. The proportions method suffered from systematic errors due to lack of proportionality between ICV and neuroanatomical volumes, leading to systematic mis-assignment of structures as either larger or smaller than their actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method. The findings in the current study explain some of the considerable variation in the literature on sexual dimorphisms in neuroanatomical volumes. In conclusion, sex plays a minor role for neuroanatomical volume differences; most differences are related to ICV.

No MeSH data available.


Related in: MedlinePlus