Heritability and reliability of automatically segmented human hippocampal formation subregions

Whelan, Christopher D.; Hibar, Derrek P.; Velzen, Laura S. van; Zannas, Anthony S.; Carrillo-Roa, Tania; McMahon, Katie L.; Prasad, Gautam; Kelly, Sinéad; Faskowitz, Joshua; deZubiracay, Greig; Iglesias, Juan Eugenio; Erp, Theo G.M. van; Frodl, Thomas; Martin, Nicholas G.; Wright, Margaret J.; Jahanshad, Neda; Schmaal, Lianne; Sämann, Philipp G.; Thompson, Paul M.

doi:10.1016/j.neuroimage.2015.12.039

Cited by 120 publications

(136 citation statements)

References 79 publications

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“…Subcortical structures are also heterogeneous and consist of functionally diverging sub-regions, such as the nuclei of the pallidum or the head and tail of the caudate. Our results are in line with a recent study by Whelan et al 24. showing that hippocampal subfields differ in their heritability.…”

Section: Discussionsupporting

confidence: 94%

Heritability of the shape of subcortical brain structures in the general population

et al. 2016

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The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.

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Section: Discussionsupporting

confidence: 94%

Heritability of the shape of subcortical brain structures in the general population

et al. 2016

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“…The heritability estimates for HF subregions observed in this study, based on Human Connectome Project (HPC), closely resemble those recently reported based on the Queensland Twins Imaging Study (QTIM): heritability for all regions, except the fimbria differed by less than 0.10 (25). One interpretation of our findings is that almost all hippocampal subfields are substantially heritable.…”

Section: Discussionsupporting

confidence: 85%

Heritability of Hippocampal Formation Sub-region Volumes

Greenspan¹,

Arakelian²,

Erp³

2016

J Neurol Neurosci

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Background Hippocampal formation (HF) volume and episodic memory performance are substantially heritable, but HF subregion heritability estimates and their possible shared genetic variance with episodic memory performance remain to be determined. Methods and findings This study provides heritability estimates for hippocampal subregions (e.g, Cornu Amonis, Subiculum, Parasubiculum, Molecular and Granule Cell Layers of the Dentate Gryus) and Total HF volumes obtained using FreeSurfer 6.0. In addition, this study assesses the heritability of object sequence and verbal episodic memory performance, and the amount of shared genetic variance between HF subregions and Total HF volume and episodic memory performance. HF volumes were obtained from high-resolution brain scans from a sample of 499 siblings (mean age±SD=30.0±3.1, 203 men), including 51 monozygotic and 46 dizygotic twin pairs and 305 non-twin siblings, collected by the Human Connectome Project (www.humanconnectome.org). Heritability estimates for HF subregions ranged from 0.42–0.87 and shared genetic variance of HF subregions with hippocampal volume was substantial (mean=0.79, range=0.50–0.98). HF subregion volumes residualized for Total HF and percent HF subregion volumes were also found to be substantially heritable (range=0.04–0.86 and 0.07–0.84, respectively). Verbal (h2=0.47) but not object sequence episodic memory was found to be significantly heritable; though the amount of shared genetic variance between HF subregions and verbal episodic memory was low (mean=0.10, range=0.01–0.20). Conclusions These findings suggest that HF subregion volumes are heritable and can be used as quantitative phenotypes in genetic association studies. The low shared genetic variance between HF subregions and verbal episodic memory suggests that quantitative trait analyses may not benefit from including both HF volume and episodic memory as bivariate traits in healthy individuals. The extent to which HF subregion volumes share genetic variance with neuropsychiatric disorders, and as such add value to our ability to identify genetic risk loci for these disorders, remains to be determined.

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“…We have previously analyzed FreeSurfer v6.0 output from different scanners with evidence that scanner heterogeneity provides robust and consistent results for hippocampal segmentation [4] and hippocampal subfield segmentation [25]. …”

Section: Discussionmentioning

confidence: 99%

Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder

et al. 2018

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Background Smaller hippocampal volume in patients with PTSD represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features. Methods Case-control cross-sectional study of US military veterans (n=282) from the Iraq and Afghanistan era were grouped into PTSD (n=142) and trauma-exposed controls (n=140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3-Tesla. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, dentate gyrus, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model. Results Significantly lower subfield volumes were associated with PTSD in left CA1 (p=.01; d=.21; uncorrected), CA3 (p=.04; d=.08; uncorrected), and right CA3 (p=.02; d=.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. Conclusions The present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.

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Heritability and reliability of automatically segmented human hippocampal formation subregions

Cited by 120 publications

References 79 publications

Heritability of the shape of subcortical brain structures in the general population

Heritability of the shape of subcortical brain structures in the general population

Heritability of Hippocampal Formation Sub-region Volumes

Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder

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