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G M Perera

Publications and source records attributed to G M Perera.

9 recordsLinked to original sources

Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation.

Circuits within the hippocampal formation are active during memory processing. Here we used functional magnetic resonance imaging (fMRI) to examine multiple sites across the long axis of the hippocampal formation while subjects performed different phases of an associative memory task, learning to associate faces with names. Viewing faces and hearing names in isolation resulted in separate hippocampal activation patterns. Pairing faces with names resulted a spatially redistributed activation pattern, rather than a simple summation of the activation patterns resulting from viewing faces and hearing names in isolation. Recalling names when cued with faces reactivated a pattern similar to that found during paired training. Finally, the activation patterns representing faces and names were found to be experience dependent, emerging with repeated exposure. Interpreted in the context of hippocampal anatomy and physiology, these findings reveal hippocampal circuit mechanisms that underlie memory encoding and retrieval.

Adult↗

Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer's disease and aging.

Memory ability declines in older age groups. There is a growing list of physiological processes that target the hippocampal formation in an age-related fashion, and some might underlie the hippocampal component of memory decline. The hippocampal formation is comprised of separate subregions, and physiological processes differentially target these subregions. The ability to evaluate the functional integrity of individual subregions-performing subregional analysis-is a major clinical goal since it can aid in the diagnosis of memory decline, as well as in elucidating mechanisms of disease and testing potential interventions. Because of its superior spatial resolution, magnetic resonance imaging (MRI) is best suited to accomplish this goal. Despite limited success, most functional MRI (fMRI) protocols have difficulty in performing complete subregional analysis of the hippocampal formation. Here we address sources of difficulty by (1) generating T2* -weighted maps of the hippocampal formation with sub-millimeter resolution; and (2) by adapting an approach used by animal investigators to identify the hippocampal subregions using anatomical landmarks. The protocol is tested in patients with Alzheimer's disease and in healthy controls, in an effort to determine whether it can detect neuronal dysfunction. Results showed diminished signal in the hippocampal formation of patients with Alzheimer's disease (AD) compared to controls, and multivariate analysis showed that this difference was most prominent in the entorhinal cortex. The protocol can be used to perform subregional analysis of the hippocampal formation. Testing the protocol in other clinical populations is needed to demonstrate its efficacy in evaluating the neuronal integrity of all hippocampal subregions.

Aged↗

Interhemispheric transfer of language in patients with left frontal cerebral arteriovenous malformation.

Cerebral arteriovenous malformations (AVMs) are frequently evaluated before therapeutic embolization by superselective injection of anesthetics into individual arterial branches so as to determine whether permanent occlusion would affect eloquent function. In Experiment 1, we used this adaptation of the Wada procedure to study three right-handed adult patients with left frontal cerebral AVMs by injecting vessels in Wernicke's and Broca's areas, respectively, and assessing language functions. The results showed that superselective testing in the inferior division of the left MCA in all three patients produced a dense Wernicke's aphasia. Injections into the left frontal regions, however, resulted in right paresis in all patients, but no language deficits including no loss of fluency. In Experiment 2, Patient 2 underwent fMRI activation for spontaneous word-list generation using multi-slice echo planar BOLD techniques at 1.5 Tesla. A voxel-by-voxel comparison of rest vs activation for each task was performed with a Z-score threshold of 2.5 SD for activated voxels. There was activation in the right hemisphere in the insula, frontal operculum pars opercularis, and inferior frontal gyrus, an area homologous to Broca's area in the left hemisphere. There was also activation in the left hemisphere in the Rolandic region, but language function was unaffected during Wada testing in this area. These data suggested that features of expressive language were no longer controlled by the left frontal lobe where the AVM was located, and provided new evidence for interhemispheric re-organization under conditions of chronic neurovascular disease.

Adult↗

Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice.

We have developed a variant of functional magnetic resonance imaging (fMRI) designed to be sensitive to static neuronal function. This method is based on resting instead of dynamic changes in oxygen-dependent signal and therefore allows for a spatial resolution that can detect signal from different hippocampal subregions in human subjects as well as in mice. We found that hippocampal signal was significantly diminished in elderly subjects with memory decline compared to age-matched controls, and different subjects showed dysfunction in different subregions. Among healthy elders, signal intensity from the subiculum was correlated selectively with memory performance. This method does not require an activation task; it can be used in anesthetized normal and in genetically modified and cognitively impaired mice. In mice the signal was found to be sufficiently sensitive to detect functional changes in the absence of underlying anatomical changes.

Aged↗

Evolution of cortical activation during recovery from corticospinal tract infarction.

BACKGROUND AND PURPOSE: Recovery from hemiparesis due to corticospinal tract infarction is well documented, but the mechanism of recovery is unknown. Functional MRI (fMRI) provides a means of identifying focal brain activity related to movement of a paretic hand. Although prior studies have suggested that supplementary motor regions in the ipsilesional and contralesional hemisphere play a role in recovery, little is known about the time course of cortical activation in these regions as recovery proceeds. METHODS: Eight patients with first-ever corticospinal tract lacunes causing hemiparesis had serial fMRIs within the first few days after stroke and at 3 to 6 months. Six healthy subjects were used as controls. Statistically significant voxels during a finger-thumb opposition task were identified with an automated image processing program. An index of ipsilateral versus contralateral activity was used to compare relative contributions of the 2 hemispheres to motor function in the acute and chronic phases after stroke. RESULTS: Controls showed expected activation in the contralateral sensorimotor cortex (SMC), premotor, and supplementary motor areas. Stroke patients differed from control patients in showing greater activation in the ipsilateral SMC, ipsilateral posterior parietal, and bilateral prefrontal regions. Compared with the nonparetic hand, the ratio of contralateral to ipsilateral SMC activity during movement of the paretic hand increased significantly over time as the paretic hand regained function. CONCLUSIONS: The evolution of activation in the SMC from early contralesional activity to late ipsilesional activity suggests that a dynamic bihemispheric reorganization of motor networks occurs during recovery from hemiparesis.

Adult↗

Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease.

The hippocampal formation is composed of separate anatomical regions interconnected to form a circuit, and investigating abnormal hippocampal function is most revealing at the level of these regions. Until recently, regional analysis of the hippocampal formation could be performed only in animals or in human postmortem tissue. Here, we report a method using functional magnetic resonance imaging that evaluates the hippocampal regions in vivo, and we use this method to study elderly with normal memory, with isolated memory decline, and with probable Alzheimer's disease (AD). Although age-related memory decline occurs commonly, the cause of this decline remains unknown, with disagreement as to whether this decline represents one or more etiologies. Analysis revealed two distinct patterns of regional dysfunction among elderly with isolated memory decline--one pattern similar to that found in elders with AD, involving all hippocampal regions, and a second pattern with dysfunction restricted to only one hippocampal region, the subiculum. These results offer direct evidence of hippocampal dysfunction associated with memory decline in the elderly, and implicate both predementia AD and non-AD processes as possible underlying causes.

Aged↗

SPECT imaging of odor identification in schizophrenia.

Deficits in olfactory identification, despite normal odor perception, are found in some neuropsychiatric disorders, including schizophrenia. We examined if regional cerebral blood flow (rCBF) differed between schizophrenia patients and controls during odor identification, hypothesizing that these brain regions could be relevant to odor identification impairments. Eight schizophrenia and eight comparison subjects provided a baseline (picture identity matching) and activation (odor identification) SPECT scan, obtained using 99mTc-HMPAO in a low dose/high dose design. Six patients and seven controls had analyzable data. MEDX data saved in ANALYZE format for SPM 95 generated paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. There was no schizophrenia vs. control group difference in rCBF for the baseline picture-matching test. For odor identification, schizophrenia patients had a hypometabolic right-sided cortical region that included the frontal lobe Broca's area, superior temporal lobe, and supramarginal and angular gyri. Post hoc within-group contrasts of picture-matching vs. odor identification showed that the controls significantly increased rCBF in the right-sided inferior temporal fusiform gyrus, and bilateral hippocampi and visual association areas for the odor test. The schizophrenia group showed no rCBF differences for picture-matching compared to odor identification. Patients showed significant hypometabolism in right-sided cortical areas for odor identification. They also failed to show increased rCBF in the hippocampus and visual association area, as seen in controls for odor identification compared to picture-matching. These regions may be unique to schizophrenia or have broader implications for olfactory memory retrieval.

Adult↗

Changes in regional cerebral blood flow related to line bisection discrimination and visual attention using HMPAO-SPECT.

Behavioral tasks requiring visual-spatial discrimination such as line bisection are used clinically to assess right hemisphere function, yet the anatomical substrate of line bisection has yet to be elucidated by functional imaging. In the current study, nine right-handed, healthy adult subjects underwent split-dose technetium-99m-hexamethylpropylene amine oxime single photon emission tomography during performance of two visual tasks. Statistical parametric maps that represented significant changes in regional cerebral blood flow (rCBF) for each task were generated. Increases in rCBF were seen in the right dorsolateral prefrontal cortex, the insula, and the superior temporal lobe with a line-bisection discrimination task, whereas increases in the visual association areas, the posterior cingulate gyrus bilaterally, and the anterior cingulate gyrus on the right were seen with a similar control task which required sustained visual attention, but no visual spatial discrimination. We conclude that distinct areas in the nondominant hemisphere can be shown to be active during performance of line-bisection discrimination and sustained visual attention.

Adult↗

MRI brain image segmentation by multi-resolution edge detection and region selection.

Combining both spatial and intensity information in image, we present an MRI brain image segmentation approach based on multi-resolution edge detection, region selection, and intensity threshold methods. The detection of white matter structure in brain is emphasized in this paper. First, a multi-resolution brain image representation and segmentation procedure based on a multi-scale image filtering method is presented. Given the nature of the structural connectivity and intensity homogeneity of brain tissues, region-based methods such as region growing and subtraction to segment the brain tissue structure from the multi-resolution images are utilized. From the segmented structure, the region-of-interest (ROI) image in the structure region is derived, and then a modified segmentation of the ROI based on an automatic threshold method using our threshold selection criterion is presented. Examples on both T1 and T2 weighted MRI brain image segmentation is presented, showing finer brain tissue structures.

Brain↗