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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

Sex differences after adjusting for ICV, age, height, and diastolic blood pressure. The bars illustrate mean standardized volume for men (blue) and women (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-matched subsample. Top right: ICV-corrected using the proportions method. Bottom left: ICV-corrected using the residuals method. Bottom right: ICV-corrected using the ANCOVA method. *Corrected p < 0.05. See Materials and Methods for details on how the covariates were included in the different models.
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Figure 8: Sex differences after adjusting for ICV, age, height, and diastolic blood pressure. The bars illustrate mean standardized volume for men (blue) and women (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-matched subsample. Top right: ICV-corrected using the proportions method. Bottom left: ICV-corrected using the residuals method. Bottom right: ICV-corrected using the ANCOVA method. *Corrected p < 0.05. See Materials and Methods for details on how the covariates were included in the different models.

Mentions: Age, height, and DBP were included as covariates in GLMs using the volumes from the ICV-matched subsample, and the residuals and proportion methods ICV-corrected volumes as dependent variables. In addition, the uncorrected neuroanatomical volumes were used as dependent variables and ICV as covariate together with age, height, and DBP in a separate ANCOVA analysis (O'brien et al., 2011). Significant results are shown in Figure 8. No significant interactions between the different covariates and sex were found, thus we report only the main effects of sex. In the ICV-matched subsample, men had larger amygdala, F(1, 298) = 15.87, p = 0.002. With the ICV-proportions method, cerebral white matter, F(1, 952) = 15.09, p = 0.001, and the 3rd ventricle, F(1, 952) = 25.01, p < 0.001, were larger in men, whereas cerebral cortex, F(1, 952) = 12.01, p = 0.002, was larger in women. With the ICV-residuals method, the amygdala, F(1, 952) = 17.27, p = 0.001, hippocampus, F(1, 952) = 20.37, p < 0.001, putamen, F(1, 952) = 19.25, p < 0.001, and thalamus, F(1, 952) = 14.24, p = 0.003, were larger in men. No structures were larger in women. Finally, in the ANCOVA models where ICV and the other covariates were entered into the same model, and the uncorrected neuroanatomical volumes were the dependent variables, the amygdala, F(1, 951) = 22.08, p < 0.001, cerebellar cortex, F(1, 951) = 13.59, p = 0.004, hippocampus, F(1, 951) = 16.84, p = 0.001, putamen, F(1, 951) = 18.34, p < 0.001, thalamus, F(1, 951) = 11.94, p = 0.007, and 3rd ventricle, F(1, 951) = 12.74, p = 0.005, were larger in men. No structures were larger in women.


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)

Sex differences after adjusting for ICV, age, height, and diastolic blood pressure. The bars illustrate mean standardized volume for men (blue) and women (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-matched subsample. Top right: ICV-corrected using the proportions method. Bottom left: ICV-corrected using the residuals method. Bottom right: ICV-corrected using the ANCOVA method. *Corrected p < 0.05. See Materials and Methods for details on how the covariates were included in the different models.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 8: Sex differences after adjusting for ICV, age, height, and diastolic blood pressure. The bars illustrate mean standardized volume for men (blue) and women (orange) with the standard error superimposed. Y-axis: Z-score of the residuals. Top left: ICV-matched subsample. Top right: ICV-corrected using the proportions method. Bottom left: ICV-corrected using the residuals method. Bottom right: ICV-corrected using the ANCOVA method. *Corrected p < 0.05. See Materials and Methods for details on how the covariates were included in the different models.
Mentions: Age, height, and DBP were included as covariates in GLMs using the volumes from the ICV-matched subsample, and the residuals and proportion methods ICV-corrected volumes as dependent variables. In addition, the uncorrected neuroanatomical volumes were used as dependent variables and ICV as covariate together with age, height, and DBP in a separate ANCOVA analysis (O'brien et al., 2011). Significant results are shown in Figure 8. No significant interactions between the different covariates and sex were found, thus we report only the main effects of sex. In the ICV-matched subsample, men had larger amygdala, F(1, 298) = 15.87, p = 0.002. With the ICV-proportions method, cerebral white matter, F(1, 952) = 15.09, p = 0.001, and the 3rd ventricle, F(1, 952) = 25.01, p < 0.001, were larger in men, whereas cerebral cortex, F(1, 952) = 12.01, p = 0.002, was larger in women. With the ICV-residuals method, the amygdala, F(1, 952) = 17.27, p = 0.001, hippocampus, F(1, 952) = 20.37, p < 0.001, putamen, F(1, 952) = 19.25, p < 0.001, and thalamus, F(1, 952) = 14.24, p = 0.003, were larger in men. No structures were larger in women. Finally, in the ANCOVA models where ICV and the other covariates were entered into the same model, and the uncorrected neuroanatomical volumes were the dependent variables, the amygdala, F(1, 951) = 22.08, p < 0.001, cerebellar cortex, F(1, 951) = 13.59, p = 0.004, hippocampus, F(1, 951) = 16.84, p = 0.001, putamen, F(1, 951) = 18.34, p < 0.001, thalamus, F(1, 951) = 11.94, p = 0.007, and 3rd ventricle, F(1, 951) = 12.74, p = 0.005, were larger in men. No structures were larger in women.

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