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Biomedical subjects

Thomas E Nichols

Publications and source records attributed to Thomas E Nichols.

9 recordsLinked to original sources

Genes regulated by learning in the hippocampus.

The enduring changes in long-term memory probably depend on regulation of gene expression in the hippocampus. To seek genes regulated by learning, we used microarray technology to compare hippocampal gene expression in mice undergoing training in the Morris water maze and control mice forced to swim for the same period in the absence of a hidden platform. ANOVA was employed to prioritize genes for further study, and three genes were confirmed by real-time PCR as being regulated during learning. One of the genes was the alpha subunit of the platelet-derived growth factor receptor (Pdgfra); another showed homology to DnaJ and cAMP response element-binding protein 2 (CREB2); and a third was novel. These genes may provide useful insights into the molecular mechanisms of hippocampal learning.

Activating Transcription Factor 4↗

Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a fMRI study.

BACKGROUND: Significant differences between individual responses to emotional stimuli can be important for the study of emotion. We investigated whether incorporating individual ratings of emotional arousal in the analysis of functional magnetic resonance imaging (fMRI) data improves the detection of activation in the medial prefrontal cortex (MPFC) and sublenticular extended amygdala (SLEA), areas implicated in the processing of emotional salience. METHODS: Healthy subjects viewed counterbalanced blocks of aversive, nonaversive, and blank images. Outside the scanner, they rated the intensity of emotional arousal (salience) of each presented picture. RESULTS: Incorporating the subject's response to each stimulus by using individualized regressors produced more robust activations within MPFC and SLEA compared with a simple boxcar regressor, identical for all subjects. CONCLUSIONS: Our findings demonstrate that individual behavioral data are useful in improving detection of activation in block-design functional imaging studies.

Adult↗

Switching attention and resolving interference: fMRI measures of executive functions.

Is there a single executive process or are there multiple executive processes that work together towards the same goal in some task? In these experiments, we use counter switching and response inhibition tasks to examine the neural underpinnings of two cognitive processes that have often been identified as potential executive processes: the switching of attention between tasks, and the resolution of interference between competing task responses. Using functional magnetic resonance imaging (fMRI), for both event-related and blocked design tasks, we find evidence for common neural areas across both tasks in bilateral parietal cortex (BA 40), left dorsolateral prefrontal cortex (DLPFC; BA 9), premotor cortex (BA 6) and medial frontal cortex (BA 6/32). However, we also find areas preferentially involved in the switching of attention between mental counts (BA 7, BA 18) and the inhibition of a prepotent motor response (BA 6, BA 10), respectively. These findings provide evidence for the separability of cognitive processes underlying executive control.

Adolescent↗

Optimization of experimental design in fMRI: a general framework using a genetic algorithm.

This article describes a method for selecting design parameters and a particular sequence of events in fMRI so as to maximize statistical power and psychological validity. Our approach uses a genetic algorithm (GA), a class of flexible search algorithms that optimize designs with respect to single or multiple measures of fitness. Two strengths of the GA framework are that (1) it operates with any sort of model, allowing for very specific parameterization of experimental conditions, including nonstandard trial types and experimentally observed scanner autocorrelation, and (2) it is flexible with respect to fitness criteria, allowing optimization over known or novel fitness measures. We describe how genetic algorithms may be applied to experimental design for fMRI, and we use the framework to explore the space of possible fMRI design parameters, with the goal of providing information about optimal design choices for several types of designs. In our simulations, we considered three fitness measures: contrast estimation efficiency, hemodynamic response estimation efficiency, and design counterbalancing. Although there are inherent trade-offs between these three fitness measures, GA optimization can produce designs that outperform random designs on all three criteria simultaneously.

Algorithms↗

Diagnosis and exploration of massively univariate neuroimaging models.

The goal of this work is to establish the validity of neuroimaging models and inferences through diagnosis and exploratory data analysis. While model diagnosis and exploration are integral parts of any statistical modeling enterprise, these aspects have been mostly neglected in functional neuroimaging. We present methods that make diagnosis and exploration of neuroimaging data feasible. We use three- and one-dimensional summaries that characterize the model fit and the four-dimensional residuals. The statistical tools are diagnostic summary statistics with tractable null distributions and the dynamic graphical tools which allow the exploration of multiple summaries in both spatial and temporal/interscan aspects, with the ability to quickly jump to spatiotemporal detail. We apply our methods to a fMRI data set, demonstrating their ability to localize subtle artifacts and to discover systematic experimental variation not captured by the model.

Algorithms↗

Nonparametric permutation tests for functional neuroimaging: a primer with examples.

Requiring only minimal assumptions for validity, nonparametric permutation testing provides a flexible and intuitive methodology for the statistical analysis of data from functional neuroimaging experiments, at some computational expense. Introduced into the functional neuroimaging literature by Holmes et al. ([1996]: J Cereb Blood Flow Metab 16:7-22), the permutation approach readily accounts for the multiple comparisons problem implicit in the standard voxel-by-voxel hypothesis testing framework. When the appropriate assumptions hold, the nonparametric permutation approach gives results similar to those obtained from a comparable Statistical Parametric Mapping approach using a general linear model with multiple comparisons corrections derived from random field theory. For analyses with low degrees of freedom, such as single subject PET/SPECT experiments or multi-subject PET/SPECT or fMRI designs assessed for population effects, the nonparametric approach employing a locally pooled (smoothed) variance estimate can outperform the comparable Statistical Parametric Mapping approach. Thus, these nonparametric techniques can be used to verify the validity of less computationally expensive parametric approaches. Although the theory and relative advantages of permutation approaches have been discussed by various authors, there has been no accessible explication of the method, and no freely distributed software implementing it. Consequently, there have been few practical applications of the technique. This article, and the accompanying MATLAB software, attempts to address these issues. The standard nonparametric randomization and permutation testing ideas are developed at an accessible level, using practical examples from functional neuroimaging, and the extensions for multiple comparisons described. Three worked examples from PET and fMRI are presented, with discussion, and comparisons with standard parametric approaches made where appropriate. Practical considerations are given throughout, and relevant statistical concepts are expounded in appendices.

Brain↗

Statistical analysis of multiplex brain gene expression images.

Analysis of variance (ANOVA) was employed to investigate 9,000 gene expression patterns from brains of both normal mice and mice with a pharmacological model of Parkinson's disease (PD). The data set was obtained using voxelation, a method that allows high-throughput acquisition of 3D gene expression patterns through analysis of spatially registered voxels (cubes). This method produces multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. The ANOVA model was compared to the results from singular value decomposition (SVD) by using the first 42 singular vectors of the data matrix, a number equal to the rank of the ANOVA model. The ANOVA was also compared to the results from non-parametric statistics. Lastly, images were obtained for a subset of genes that emerged from the ANOVA as significant. The results suggest that ANOVA will be a valuable framework for insights into the large number of gene expression patterns obtained from voxelation.

Analysis of Variance↗

Spatiotemporal reconstruction of list-mode PET data.

We describe a method for computing a continuous time estimate of tracer density using list-mode positron emission tomography data. The rate function in each voxel is modeled as an inhomogeneous Poisson process whose rate function can be represented using a cubic B-spline basis. The rate functions are estimated by maximizing the likelihood of the arrival times of detected photon pairs over the control vertices of the spline, modified by quadratic spatial and temporal smoothness penalties and a penalty term to enforce nonnegativity. Randoms rate functions are estimated by assuming independence between the spatial and temporal randoms distributions. Similarly, scatter rate functions are estimated by assuming spatiotemporal independence and that the temporal distribution of the scatter is proportional to the temporal distribution of the trues. A quantitative evaluation was performed using simulated data and the method is also demonstrated in a human study using 11C-raclopride.

Algorithms↗