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Biomedical subjects

T Cizadlo

Publications and source records attributed to T Cizadlo.

At least 19 recordsLinked to original sources

Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging.

Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.

Adolescent↗

Measurement of brain structures with artificial neural networks: two- and three-dimensional applications.

PURPOSE: To evaluate the ability of an artificial neural network (ANN) to identify brain structures. This ANN was applied to postprocessed magnetic resonance (MR) images to segment various brain structures in both two- and three-dimensional applications. MATERIALS AND METHODS: An ANN was designed that learned from experience to define the corpus callosum, whole brain, caudate, and putamen. Manual segmentation was used as a training set for the ANN. The ANN was trained on two-thirds of the manually segmented images and was tested on the remaining one-third. The reliability of the ANN was compared against manual segmentations by two technicians. RESULTS: The ANN was able to identify the brain structures as readily and as well as did the two technicians. Reliability of the ANN compared with the technicians was 0.96 for the corpus callosum, 0.95 for the whole brain, 0.86 (right) and 0.93 (left) for the caudate, and 0.71 (right) and 0.88 (left) for the putamen. CONCLUSION: The ANN was able to identify the structures used in this study as well as did the two technicians. The ANN could do this much more rapidly and without rater drift. Several other cortical and subcortical structures could also be readily identified with this method.

Adult↗

The cerebellum plays a role in conscious episodic memory retrieval.

The cerebellum has traditionally been considered to be primarily dedicated to motor functions. Its phylogenetic development and connectivity suggest, however, that it also may play a role in cognitive processes in the human brain. In order to examine a potential cognitive role for the cerebellum in human beings, a positron emission tomography (PET) study was conducted during a "pure thought experiment": subjects intentionally recalled a specific past personal experience (consciously retrieved episodic memory). Since there was no motor or sensory input or output, the design eliminated the possibility that cerebellar changes in blood flow were due to motor activity. During silent recall of a consciously retrieved episodic memory, activations were observed in the right lateral cerebellum, left medial dorsal thalamus, medial and left orbital frontal cortex, anterior cingulate, and a left parietal region. These activations confirm a cognitive role for the cerebellum, which may participate in an interactive cortical-cerebellar network that initiates and monitors the conscious retrieval of episodic memory.

Adult↗

An efficient procedure for permutation tests in imaging research.

Recent interest in hypothesis testing on functional imaging data has spurred the development of several statistical techniques. The purpose of this paper is to provide a method to reduce the computational intensity associated with randomization tests of positron emission tomography imaging data. We discuss the advantages and disadvantages of traditional distributional hypothesis testing versus the advantages and disadvantages of randomization tests. A method for reducing the computational intensity of randomization uses a conjunction of updating and sequenching and results in significantly reduced processing. The running times of randomization methods are compared.

Algorithms↗

Functional MRI statistical software packages: a comparative analysis.

Currently, there are many choices of software packages for the analysis of fMRI data, each offering many options. Since no one package can meet the needs of all fMRI laboratories, it is helpful to know what each package offers. Several software programs were evaluated for comparison of their documentation, ease of learning and use, referencing, data input steps required, types of statistical methods offered, and output choices. The functionality of each package was detailed and discussed. AFNI 2.01, SPM96, Stimulate 5.0, MEDIMAX 2.01, and FIT were tested. FIASCO, Yale, and MEDx 2.0 were described but not tested. A description of each package is provided.

Algorithms↗

A method to determine activation thresholds in fMRI paradigms.

Determining meaningful activation thresholds in functional magnetic resonance imaging (fMRI) paradigms is complicated by several factors. These include the time-series nature of the data, the influence of physiological rhythms (e.g. respiration) and vacillations introduced by the experimental design (e.g. cueing). We present an empirical threshold for each subject and each fMRI experiment that takes these factors into account. The method requires an additional fMRI data set as similar to the experimental paradigm as possible without dichotomously varying the experimental task of interest. A letter fluency task was used to illustrate this method. This technique differs from classical methods since the Pearson correlation probability values tabulated from statistical theory are not used. Rather each subject defines his or her own set of threshold probability values for correlations. It is against these empirical thresholds, not Pearson's, that an experimental fMRI correlation is assessed.

Adult↗

Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.

Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

Adult↗

Landmark-based registration and measurement of magnetic resonance images: a reliability study.

We report a magnetic resonance imaging (MRI) study in a large number of subjects that examines various analytic techniques for anatomical landmark information. The initial issue involved interrater reliability in locating landmarks along the midsagittal plane. Another issue dealt with using landmarks to register (linear) individual scans for subsequent analyses or more sophisticated registration techniques. We next explore the use of interlandmark distances as indices of brain size. Twenty-seven landmarks were chosen from the midsagittal slice of 101 abnormal subjects. Interrater reliability estimates on a subset of the scans were excellent overall. Rotating to anterior-posterior commissure points was the best of the tested two-point registrations, although an average angular rotation was better. Reliability and validity for landmark-derived measures of size were excellent. Landmark-based analyses offer opportunities to explore shape and size questions, although they are not appropriate for addressing all questions. Under specific conditions, landmark data can be generated quickly and accurately.

Adolescent↗

Auditory attentional deficits in patients with schizophrenia. A positron emission tomography study.

BACKGROUND: Patients with schizophrenia have frequently been found to perform poorly on tasks requiring selective attention, defined as the ability to focus attention on relevant information while simultaneously ignoring irrelevant stimuli. This study explores the brain mechanisms mediating attentional processing in patients with schizophrenia by measuring their regional cerebral blood flow (rCBF) with positron emission tomography using [15O] water as they performed tasks that differed systematically in attentional demand. METHODS: Ten schizophrenic patients (either neurolepticnaive or withdrawn from medication) (patient group) and 10 normal volunteers (control group) performed auditory target detection tasks. Different types of auditory stimuli (environmental sounds, meaningless speech sounds, and words) were presented either binaurally (ie, same sounds in both ears) or dichotically (simultaneous and different sounds in the 2 ears). In dichotic conditions, subjects were instructed to focus on either their left or right ear. RESULTS: Initial subtraction-based image analyses sought significant rCBF changes anywhere in the brain. Patients consistently had less significant activation than controls in right superotemporal gyrus (STG). Follow-up analyses used regions of interest traced on individual magnetic resonance images to precisely measure rCBF in STG. Unlike controls, patients had higher rCBF in the left STG during all activation conditions. CONCLUSIONS: The abnormal task-related rCBF asymmetry in STG of schizophrenic patients may indicate an isolated temporal lobe deficit, but it may also indicate abnormality in the thalamocortical circuitry mediating selective attention and/or in the brain systems that integrate auditory processing in the 2 hemispheres.

Adult↗

Normalizing counts and cerebral blood flow intensity in functional imaging studies of the human brain.

Image intensity normalization is frequently applied to eliminate or adjust for subject or injection global blood flow (gCBF) and other sources of nuisance variation. Normalization has several other positive effects on the analysis of PET images. However, the choice of an intensity normalization technique affects the statistical and psychometric properties of the image data. We compared three normalization procedures, the ratio approach (regional (r)CBF/gCBF), histogram equalization, and ANCOVA, on both PET count and flow data sets. The ratio method presents the proportional increase of regions, the histogram equalization method offers the relative ranking of intensities over the image, and the ANCOVA method provides statistical deviations from an expected linear model of regional values from the subject's gCBF. The original study used 33 normal subjects in a standard subtraction paradigm. The normalization methods were evaluated on their ability to remove extraneous error variation, induce homogeneity of intersubject variation, and remove unwanted dependencies. In general, the normalization modified the subtraction image more than the individual condition images. All three methods worked well at removing the dependency of rCBF on gCBF in count and flow images. For count data, the three methods also reduced the amount of error variation equally well, improving the signal to noise ratio. For flow data, the histogram equalization and ratio methods worked best at reducing statistical error. All three methods dramatically stabilized the variance over the image.

Analysis of Variance↗

Sample size and statistical power in [15O]H2O studies of human cognition.

Determining the appropriate sample size is a crucial component of positron emission tomography (PET) studies. Power calculations, the traditional method for determining sample size, were developed for hypothesis-testing approaches to data analysis. This method for determining sample size is challenged by the complexities of PET data analysis: use of exploratory analysis strategies, search for multiple correlated nodes on interlinked networks, and analysis of large numbers of pixels that may have correlated values due to both anatomical and functional dependence. We examine the effects of variable sample size in a study of human memory, comparing large (n = 33), medium (n = 16,17), small (n = 11, 11, 11), and very small (n = 6,6,7,7,7) samples. Results from the large sample are assumed to be the "gold standard." The primary criterion for assessing sample size is replicability. This is evaluated using a hierarchically ordered group of parameters: pattern of peaks, location of peaks, number of peaks, size (volume) of peaks, and intensity of the associated t (or z) statistic. As sample size decreases, false negatives begin to appear, with some loss of pattern and peak detection; there is no corresponding increase in false positives. The results suggest that good replicability occurs with a sample size of 10-20 subjects in studies of human cognition that use paired subtraction comparisons of single experimental/baseline conditions with blood flow differences ranging from 4 to 13%.

Adult↗

Tests for comparing images based on randomization and permutation methods.

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question "Are two image sets different?" The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.

Computer Simulation↗

Neural substrates of facial recognition.

Seventeen healthy normal volunteers performed three facial recognition tasks while their cerebral blood flow was measured with PET: categorizing faces according to gender, recognizing new faces, and recognizing familiar faces. These tasks activated three different pathways: respectively, the left inferior temporal lobe and left frontal cortex; a predominantly right frontal-right parietal-left cerebellar network; and left lingual and left and right fusiform gyri. These results suggest that humans use different brain regions in performing these three routine daily activities. The results are consistent with previous observations concerning organization of extrastriate visual cortex in human and nonhuman primate lesion studies, including studies of the unusual syndrome of prosopagnosia (loss of the ability to recognize familiar faces with intact ability to recognize a face as a face).

Adult↗

Short-term and long-term verbal memory: a positron emission tomography study.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.

Adult↗

I. PET studies of memory: novel and practiced free recall of complex narratives.

Positron Emission Tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers during two experimental memory tasks, one of which was well-practiced and the other of which was novel. The materials used for the memory tasks consisted of two complex narratives (Story A and Story B from the Wechsler Memory Scale). Natural language materials were chosen because they similate experimentally the natural learning situation and permit study of the neural mechanisms by which recall memory becomes more fluid, automatic, or "rote." One week before the PET study, subjects were trained to perfect recall of Story A, while they were exposed to Story B only 60 s prior to PET data acquisition. Despite the substantial differences in level of familiarity (and in free recall performance), patterns of activation were quite similar; activations presumed to reflect recall in both tasks included frontal, inferior temporal, thalamic, anterior cingulate, and cerebellar regions. Many regions were smaller during recall of the familiar story, however, presumably reflecting greater neural efficiency due to practice. In addition, the novel task activated an additional left frontal region that is presumed to reflect more active encoding. The similarity and multiplicity of the activations in the two tasks suggest that the brain uses a multinodal general network for memory tasks such as free recall, while the differences suggest that some nodes in the network may be used for specific components of memory such as encoding and retrieval.

Adult↗

II. PET studies of memory: novel versus practiced free recall of word lists.

Positron emission tomography (PET) with the tracer H215O was used to measure regional cerebral blood flow in 13 healthy volunteers while they engaged in free recall of 15-item word lists from the Rey Auditory Verbal Learning task. The study was designed so that recall of well-practiced versus novel material could be compared. One week before the PET study, subjects were trained to perfect recall of List A, while they were exposed to list B only 60 s prior to PET data acquisition. As in the companion study of free recall of complex narratives, we observed that practice tended to decrease the size of activations in regions involved in the memory component of the task; we also observed that the novel recall task produced greater activation in left frontal regions, probably due to active encoding. A commonality of other regions observed in this pair of studies, as well as other studies of memory in the literature, suggests that the human brain may contain a distributed multinodal general memory system. Nodes on this network include the frontal, parietal, and temporal cortices, the thalamus, the anterior and posterior cingulate, the precuneus, and the cerebellum. There appears to be a commonality of components across tasks (e.g., retrieval, encoding) that is independent of content, as well as differentiation of some components that may be content-specific or tasks-specific. In addition, these results support a significant role for the cerebellum in cognitive functions such as memory.

Adult↗

Multi-center N400 ERP consistency using a primed and unprimed word paradigm.

A word priming paradigm involving primed, unprimed, and non-word experimental conditions was used to elicit event-related potentials (ERPs) in normal, young adult males in identically equipped electrophysiology laboratories located in 6 different cities in the USA. Analyses of the average amplitude of a specified latency window containing the N400, the N400 peak amplitude, or the latency of the N400 peak amplitude found no differences among laboratory locations. The shape of the N400 ERP wave form was also found to be highly correlated across laboratory sites for each experimental condition. Comparison of the data with analogous word priming paradigms revealed similar patterns for the N400 components and response times in both the primed and unprimed experimental conditions. These findings suggest that the data from all 6 laboratory locations are consistent with each other and are congruous with those found in other N400 studies and will permit pooling of subject data for future research.

Adolescent↗

Abnormalities in midline attentional circuitry in schizophrenia: evidence from magnetic resonance and positron emission tomography.

The syndrome of schizophrenia presents with a complex array of symptoms that are difficult to explain at the neural level. Data collected using magnetic resonance (MR) and positron emission tomography (PET) suggest that this complex array could occur as a consequence of misconnections and mismatches in midline circuitry that is reticular-thalamic-cingulate-cortical. MR studies have shown a variety of abnormalities, including callosal agenesis, cavum septi pellucidi, decreased thalamic size, decreased frontal size, and changes in signal intensity in white matter tracts between the thalamus and the frontal cortex. PET studies using a dichotic listening paradigm suggest that patients suffering from schizophrenia have brain blood flow abnormalities consistent with a difficulty in focusing or shifting attention, which may reflect the functional substrate of the anatomic abnormalities.

Attention↗