Incomplete Hippocampal Inversion and Its Relationship to Hippocampal Subfield Volumes and Aging

Colenutt, Jessica; McCann, Bryony; Knight, Michael; Coulthard, Elizabeth; Kauppinen, Risto A.

doi:10.1111/jon.12509

Cited by 9 publications

(15 citation statements)

References 23 publications

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“…This work is ongoing and will serve as the basis for new validation experiments within the MRI domain (Olsen et al, 2019). The influence of incomplete hippocampal inversion -a common, atypical rotation of the hippocampal formation (Cury et al, 2015) that impacts subfield volumes (Colenutt et al, 2018) -presents another challenge.…”

Section: Summary Discussion and Outlookmentioning

confidence: 99%

“…Following this logic, most subjects in this category do not need to be excluded. Research on the effect of known normal variants is ongoing; more recently, a correlation between CA1 volumes and incomplete hippocampal inversion (IHI), a very common normal variant found in about 20% of healthy subjects (Colenutt et al, 2018), has been reported.…”

Section: Theoretical Considerations For Qcmentioning

confidence: 99%

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FreeSurfer based segmentation of hippocampal subfields: a review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Sämann¹,

Iglesias²,

Gutman³

et al. 2020

Preprint

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Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and even variation within the normal range is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the ENIGMA Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with major depressive disorder, bipolar disorders, posttraumatic stress disorder, and other conditions, along with data from matched controls. In this overview, we explain the algorithm’s principle, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modelled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, schizophrenia, childhood trauma and posttraumatic stress disorder, inflammatory and systemic disease, alcoholism, stress regulation, neurotoxicity, as well as assessments of heritability, effects of candidate genes, genome-wide association studies and epigenetic effects. Lastly, we highlight points where FreeSurfer-based hippocampal subfield studies may be optimized.

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Section: Summary Discussion and Outlookmentioning

confidence: 99%

Section: Theoretical Considerations For Qcmentioning

confidence: 99%

FreeSurfer based segmentation of hippocampal subfields: a review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Sämann¹,

Iglesias²,

Gutman³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Recently, Cury et al established a clear set of quantitative IHI criteria in a large healthy cohort [20]. Subsequent studies using these criteria reported consistent prevalence estimates and findings [36,37]. Employing the Cury criteria, the prevalence of IHI can now be reliably assessed in neuropsychiatric disorders such as schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the hippocampal volumes of participants with IHI did not differ from those without the variant. In a second study analyzing a healthy, aging cohort, the authors reported that participants with IHI do not differ in whole hippocampal volume, but show decreased subfield volumes, namely CA1 [37]. However, IHI lowers the accuracy of automated segmentation protocols, making it difficult to assess the effect of IHI on subfield volume estimates [39].…”

Section: Introductionmentioning

confidence: 99%

Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure

et al. 2021

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Incomplete hippocampal inversion (IHI) is an anatomical variant of the human brain resulting from an arrest in brain development, especially prevalent in the left hemisphere. We hypothesized that IHI is more common in schizophrenia and contributes to the well-known hippocampal structural differences. We studied 199 schizophrenia patients and 161 healthy control participants with 3 T MRI to establish IHI prevalence and the relationship of IHI with hippocampal volume and asymmetry. IHI was more prevalent (left hemisphere: 15% of healthy control participants, 27% of schizophrenia patients; right hemisphere: 4% of healthy control participants, 10% of schizophrenia patients) and more severe in schizophrenia patients compared to healthy control participants. Severe IHI cases were associated with a higher rate of automated segmentation failure. IHI contributed to smaller hippocampal volume and increased R > L volume asymmetry in schizophrenia. The increased prevalence and severity of IHI supports the neurodevelopmental model of schizophrenia. The impact of this developmental variant deserves further exploration in studies of the hippocampus in schizophrenia.

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“…IHIs are mainly left-sided and characterized by a rounded or vertical shape, a medial positioning and a deep collateral sulcus [13][14][15] and are present in around 20% of the normal population [15]. It has been reported that IHI impacts the hippocampal volume: subjects with incomplete inversions appear to have smaller hippocampi [16], and more specifically, the hippocampal subfield CA1 seems to be related to the IHI severity [17]. Also it has been suggested that IHI might interfere with the quality of hippocampal segmentation for volumetric analysis [16,18], which may be clinically relevant, since the hippocampal volume can predict the response to antidepressant in patients without IHI [4,5].…”

Section: Introductionmentioning

confidence: 99%

Genome wide association study of incomplete hippocampal inversion in adolescents

Cury¹,

Scelsi²,

Toro³

et al. 2020

PLoS ONE

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Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h 2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013. PLOS ONE | https://doi.org/10.1371/journal.pone.

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Incomplete Hippocampal Inversion and Its Relationship to Hippocampal Subfield Volumes and Aging

Abstract: The rates of IHI prevalence in the current cohort are similar to those previously reported in healthy cohorts. The IHI severity is related to hippocampal subfield volumes, most notably the CA1, which is a novel finding with potential implications in research on aging and dementia.

Cited by 9 publications

References 23 publications

FreeSurfer based segmentation of hippocampal subfields: a review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

FreeSurfer based segmentation of hippocampal subfields: a review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Incomplete hippocampal inversion in schizophrenia: prevalence, severity, and impact on hippocampal structure

Genome wide association study of incomplete hippocampal inversion in adolescents

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