Spatial encoding in primate hippocampus during free navigation.

The hippocampus comprises two neural signals-place cells and θ oscillations-that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue. We report place cells in marmoset hippocampus during free navigation that exhibit remarkable parallels to analogous neurons in other mammalian species. Although θ oscillations were prevalent in the marmoset hippocampus, the patterns of activity were notably different than in other taxa. This local field potential oscillation occurred in short bouts (approximately .4 s)-rather than continuously-and was neither significantly modulated by locomotion nor consistently coupled to place-cell activity. These findings suggest that the relationship between place-cell activity and θ oscillations in primate hippocampus during free navigation differs substantially from rodents and paint an intriguing comparative picture regarding the neural basis of spatial navigation across mammals

Removing inter-subject technical variability in magnetic resonance imaging studies

Magnetic resonance imaging (MRI) intensities are acquired in arbitrary units, making scans non-comparable across sites and between subjects. Intensity normalization is a first step for the improvement of comparability of the images across subjects. However, we show that unwanted inter-scan variability associated with imaging site, scanner effect and other technical artifacts is still present after standard intensity normalization in large multi-site neuroimaging studies. We propose RAVEL (Removal of Artificial Voxel Effect by Linear regression), a tool to remove residual technical variability after intensity normalization. As proposed by SVA and RUV [Leek and Storey, 2007, 2008, Gagnon-Bartsch and Speed, 2012], two batch effect correction tools largely used in genomics, we decompose the voxel intensities of images registered to a template into a biological component and an unwanted variation component. The unwanted variation component is estimated from a control region obtained from the cerebrospinal fluid (CSF), where intensities are known to be unassociated with disease status and other clinical covariates. We perform a singular value decomposition (SVD) of the control voxels to estimate factors of unwanted variation. We then estimate the unwanted factors using linear regression for every voxel of the brain and take the residuals as the RAVEL-corrected intensities. We assess the performance of RAVEL using T1-weighted (T1-w) images from more than 900 subjects with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), as well as healthy controls from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We compare RAVEL to intensity-normalization-only methods, histogram matching, and White Stripe. We show that RAVEL performs best at improving the replicability of the brain regions that are empirically found to be most associated with AD, and that these regions are significantly more present in structures impacted by AD (hippocampus, amygdala, parahippocampal gyrus, enthorinal area and fornix stria terminals). In addition, we show that the RAVEL-corrected intensities have the best performance in distinguishing between MCI subjects and healthy subjects by using the mean hippocampal intensity (AUC=67%), a marked improvement compared to results from intensity normalization alone (AUC=63% and 59% for histogram matching and White Stripe, respectively). RAVEL is generalizable to many imaging modalities, and shows promise for longitudinal studies. Additionally, because the choice of the control region is left to the user, RAVEL can be applied in studies of many brain disorders

Patch-based segmentation with spatial context for medical image analysis

Accurate segmentations in medical imaging form a crucial role in many applications from pa- tient diagnosis to population studies. As the amount of data generated from medical images increases, the ability to perform this task without human intervention becomes ever more de- sirable. One approach, known broadly as atlas-based segmentation, is to propagate labels from images which have already been manually labelled by clinical experts. Methods using this ap- proach have been shown to be e ective in many applications, demonstrating great potential for automatic labelling of large datasets. However, these methods usually require the use of image registration and are dependent on the outcome of the registration. Any registrations errors that occur are also propagated to the segmentation process and are likely to have an adverse e ect on segmentation accuracy. Recently, patch-based methods have been shown to allow a relaxation of the required image alignment, whilst achieving similar results. In general, these methods label each voxel of a target image by comparing the image patch centred on the voxel with neighbouring patches from an atlas library and assigning the most likely label according to the closest matches. The main contributions of this thesis focuses around this approach in providing accurate segmentation results whilst minimising the dependency on registration quality. In particular, this thesis proposes a novel kNN patch-based segmentation framework, which utilises both intensity and spatial information, and explore the use of spatial context in a diverse range of applications. The proposed methods extend the potential for patch-based segmentation to tolerate registration errors by rede ning the \locality" for patch selection and comparison, whilst also allowing similar looking patches from di erent anatomical structures to be di erentiated. The methods are evaluated on a wide variety of image datasets, ranging from the brain to the knees, demonstrating its potential with results which are competitive to state-of-the-art techniques.Open Acces

Output order and variability in free recall are linked to cognitive ability and hippocampal volume in elderly individuals.

Adapted from the work of Kahana and colleagues (e.g., Kahana, 1996), we present two measures of order of recall in neuropsychological free recall tests. These are the position on the study list of the first recalled item, and the degree of variability in the order in which items are reported at test (i.e., the temporal distance across the first four recalled items). We tested two hypotheses in separate experiments: (1) whether these measures predicted generalized cognitive ability, and (2) whether they predicted gray matter hippocampal volume. To test hypothesis 1, we conducted ordinal regression analyses on data from a group of 452 participants, aged 60 or above. Memory performance was measured with Rey's AVLT and generalized cognitive ability was measured with the MMSE test. To test hypothesis 2, we conducted a linear regression analysis on data from a sample of 79 cognitively intact individuals aged 60 or over. Memory was measured with the BSRT and hippocampal volume was extracted from MRI images. Results of Experiment 1 showed that the position of the first item recalled and the degree of output order variability correlated with MMSE scores only in the delayed test, but not in the immediate test. In Experiment 2, the degree of variability in the recall sequence of the delayed trial correlated (negatively) with hippocampal size. These findings confirm the importance of delayed primacy as a marker of cognitive ability, and are consistent with the idea that the hippocampus is involved in coding the temporal context of learned episodes

Efficient automatic correction and segmentation based 3D visualization of magnetic resonance images

In the recent years, the demand for automated processing techniques for digital medical image volumes has increased substantially. Existing algorithms, however, still often require manual interaction, and newly developed automated techniques are often intended for a narrow segment of processing needs. The goal of this research was to develop algorithms suitable for fast and effective correction and advanced visualization of digital MR image volumes with minimal human operator interaction. This research has resulted in a number of techniques for automated processing of MR image volumes, including a novel MR inhomogeneity correction algorithm derivative surface fitting (dsf), automatic tissue detection algorithm (atd), and a new fast technique for interactive 3D visualization of segmented volumes called gravitational shading (gs). These newly developed algorithms provided a foundation for the automated MR processing pipeline incorporated into the UniViewer medical imaging software developed in our group and available to the public. This allowed the extensive testing and evaluation of the proposed techniques. Dsf was compared with two previously published methods on 17 digital image volumes. Dsf demonstrated faster correction speeds and uniform image quality improvement in this comparison. Dsf was the only algorithm that did not remove anatomic detail. Gs was compared with the previously published algorithm fsvr and produced rendering quality improvement while preserving real-time frame-rates. These results show that the automated pipeline design principles used in this dissertation provide necessary tools for development of a fast and effective system for the automated correction and visualization of digital MR image volumes

Statistical group differences in anatomical shape analysis using Hotelling T2 Metric

journal articleShape analysis has become of increasing interest to the neuroimaging community due to its potential to precisely locate morphological changes between healthy and pathological structures. This manuscript presents a comprehensive set of tools for the computation of 3D structural statistical shape analysis. It has been applied in several studies on brain morphometry, but can potentially be employed in other 3D shape problems. Its main limitations is the necessity of spherical topology. The input of the proposed shape analysis is a set of binary segmentation of a single brain structure, such as the hippocampus or caudate. These segmentations are converted into a corresponding spherical harmonic description (SPHARM), which is then sampled into a triangulated surfaces (SPHARM-PDM). After alignment, differences between groups of surfaces are computed using the Hotelling T2 two sample metric. Statistical pvalues, both raw and corrected for multiple comparisons, result in significance maps. Additional visualization of the group tests are provided via mean difference magnitude and vector maps, as well as maps of the group covariance information. The correction for multiple comparisons is performed via two separate methods that each have a distinct view of the problem. The first one aims to control the family-wise error rate (FWER) or false-positives via the extrema histogram of non-parametric permutations. The second method controls the false discovery rate and results in a less conservative estimate of the false-negatives. Prior versions of this shape analysis framework have been applied already to clinical studies on hippocampus and lateral ventricle shape in adult schizophrenics. The novelty of this submission is the use of the Hotelling T2 two-sample group difference metric for the computation of a template free statistical shape analysis. Template free group testing allowed this framework to become independent of any template choice, as well as it improved the sensitivity of our method considerably. In addition to our existing correction methodology for the multiple comparison problem using non-parametric permutation tests, we have extended the testing framework to include False Discovery Rate (FDR). FDR provides a significance correction with higher sensitivity while allowing a expected minimal amount of false-positives compared to our prior testing scheme