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E Zarahn

Publications and source records attributed to E Zarahn.

17 recordsLinked to original sources
PubMed1999

The effect of normal aging on the coupling of neural activity to the bold hemodynamic response.

The use of functional neuroimaging to test hypotheses regarding age-related changes in the neural substrates of cognitive processes relies on assumptions regarding the coupling of neural activity to neuroimaging signal. Differences in neuroimaging signal response between young and elderly subjects can be mapped directly to differences in neural response only if such coupling does not change with age. Here we examined spatial and temporal characteristics of the BOLD fMRI hemodynamic response in primary sensorimotor cortex in young and elderly subjects during the performance of a simple reaction time task. We found that 75% of elderly subjects (n = 20) exhibited a detectable voxel-wise relationship with the behavioral paradigm in this region as compared to 100% young subjects (n = 32). The median number of suprathreshold voxels in the young subjects was greater than four times that of the elderly subjects. Young subjects had a slightly greater signal:noise per voxel than the elderly subjects that was attributed to a greater level of noise per voxel in the elderly subjects. The evidence did not support the idea that the greater head motion observed in the elderly was the cause of this greater voxel-wise noise. There were no significant differences between groups in either the shape of the hemodynamic response or in its the within-group variability, although the former evidenced a near significant trend. The overall finding that some aspects of the hemodynamic coupling between neural activity and BOLD fMRI signal change with age cautions against simple interpretations of the results of imaging studies that compare young and elderly subjects.

Adolescent↗
PubMed1999

Stochastic designs in event-related fMRI.

This article considers the efficiency of event-related fMRI designs in terms of the optimum temporal pattern of stimulus or trial presentations. The distinction between "stochastic" and "deterministic" is used to distinguish between designs that are specified in terms of the probability that an event will occur at a series of time points (stochastic) and those in which events always occur at prespecified time (deterministic). Stochastic designs may be "stationary," in which the probability is constant, or nonstationary, in which the probabilities change with time. All these designs can be parameterized in terms of a vector of occurrence probabilities and a prototypic design matrix that embodies constraints (such as the minimum stimulus onset asynchrony) and the model of hemodynamic responses. A simple function of these parameters is presented and used to compare the relative efficiency of different designs. Designs with slow modulation of occurrence probabilities are generally more efficient than stationary designs. Interestingly the most efficient design is a conventional block design. A critical point, made in this article, is that the most efficient design for one effect may not be the most efficient for another. This is particularly important when considering evoked responses and the differences among responses. The most efficient designs for evoked responses, as opposed to differential responses, require trial-free periods during which baseline levels can be attained. In the context of stochastic, rapid-presentation designs this is equivalent to the inclusion of "null events."

Arousal↗
PubMed1999

Temporal isolation of the neural correlates of spatial mnemonic processing with fMRI.

The use of cognitive subtraction to study the neural substrates of the maintenance component of spatial working memory in humans relies upon the assumptions of the pure insertion of cognitive processes and a linear transform of neural activity to neuroimaging signal. Here, functional changes attributable to the memory requiring phase (referred to as the retention delay) of a spatial working memory task were temporally discriminated from those attributable to other behavioral subcomponents within trials using an experimental design that is argued to obviate these assumptions, as well as permit a joint test of their validity. The hypothesis that the assumptions of cognitive subtraction (as applied to neuroimaging) hold in general was not supported. Functional changes attributable to the retention delay were detected in the dorsolateral prefrontal cortex as well as in other cortical regions in a subset of the subjects, and in the right frontal eye field and right superior parietal lobule of all subjects (n=5). These results support models in which these regions are involved in maintaining spatial representations in humans. In addition, nearly all regions that evidenced such functional changes during the retention delay also evidenced functional changes during behaviors that did not require spatial working memory. This result tends to dispute models which posit the existence of gross neuroanatomical regions involved in solely mnemonic function.

Adult↗
PubMed1999

Event-related functional MRI: implications for cognitive psychology.

Functional magnetic resonance imaging (fMRI) has rapidly emerged as a powerful technique in cognitive neuroscience. We describe and critique a new class of imaging experimental designs called event-related fMRI that exploit the temporal resolution of fMRI by modeling fMRI signal changes associated with behavioral trials as opposed to blocks of behavioral trials. Advantages of this method over block designs include the ability to (a) randomize trial presentations, (b) test for functional correlates of behavioral measures with greater power, (c) directly examine the neural correlates of temporally dissociable components of behavioral trials (e.g., the delay period of a working memory task), and (d) test for differences in the onset time of neural activity evoked by different trial types. Consequently, event-related fMRI has the potential to address a number of cognitive psychology questions with a degree of inferential and statistical power not previously available.

Arousal↗
PubMed1998

Neural components of topographical representation.

Studies of patients with focal brain damage suggest that topographical representation is subserved by dissociable neural subcomponents. This article offers a condensed review of the literature of "topographical disorientation" and describes several functional MRI studies designed to test hypotheses generated by that review. Three hypotheses are considered: (i) The parahippocampal cortex is critically involved in the acquisition of exocentric spatial information in humans; (ii) separable, posterior, dorsal, and ventral cortical regions subserve the perception and long term representation of position and identity, respectively, of landmarks; and (iii) there is a distinct area of the ventral occipitotemporal cortex that responds maximally to building stimuli and may play a role in the perception of salient landmarks. We conclude with a discussion of the inferential limitations of neuroimaging and lesion studies. It is proposed that combining these two approaches allows for inferences regarding the computational involvement of a neuroanatomical substrate in a given cognitive process although neither method can strictly support this conclusion alone.

Agnosia↗
PubMed1998

A critique of the use of the Kolmogorov-Smirnov (KS) statistic for the analysis of BOLD fMRI data.

The use of the Kolmogorov-Smirnov (KS) statistic for testing hypotheses regarding activation in blood oxygenation level-dependent functional MRI data is critiqued on both theoretical and empirical grounds. Theoretically, it is argued that the KS test is formally unable to support inferences of interest to most neuro-imaging studies and has reduced sensitivity compared with parametric alternatives. Empirically, false-positive rates yielded by the KS test in human data collected under the null hypothesis were significantly in excess of tabular values. These excessive false-positive rates could be explained by the presence of temporal autocorrelation. We also present evidence that the distribution of blood oxygenation level-dependent functional MRI data is only slightly nonnormal, questioning the initial impetus for the use of the KS test in this context. Finally, it is noted that parametric alternatives exist that do provide adequate control of the false-positive rate and can support inferences of interest.

Algorithms↗
PubMed1998

Human prefrontal cortex is not specific for working memory: a functional MRI study.

Lesion studies in monkeys have provided evidence that lateral prefrontal cortex is necessary for working memory, the cognitive processes involved in the temporary maintenance and manipulation of information. Monkey electrophysiological studies, however, have also observed prefrontal neuronal activity associated with cognitive processes that are nonmnemonic. We tested the hypothesis that the same regions of human prefrontal cortex that demonstrate activity during working memory tasks would also demonstrate activity during tasks without working memory demands. During echoplanar fMRI imaging, subjects performed a three-condition experiment (working memory task, nonworking memory task, rest). In the working memory task, subjects observed serially presented stimuli and determined if each stimulus was the same as that presented two stimuli back. The nonworking memory task in Experiment 1 required subjects to identify a single predetermined stimulus; in Experiment 2, subjects were required to make a button press to every stimulus. In all subjects in both experiments, the working memory task exhibited greater prefrontal cortical activity compared to either nonworking memory task. In these same prefrontal regions, greater activation was also observed during both nonworking memory tasks compared to rest. We conclude that human lateral prefrontal cortex supports processes in addition to working memory. Thus, reverse inference of the form "if prefrontal cortex is active, working memory is engaged" is not supported.

Adult↗
PubMed1998

The variability of human, BOLD hemodynamic responses.

Cerebral hemodynamic responses to brief periods of neural activity are delayed and dispersed in time. The specific shape of these responses is of some importance to the design and analysis of blood oxygenation level-dependent (BOLD), functional magnetic resonance imaging (fMRI) experiments. Using fMRI scanning, we examine here the characteristics and variability of hemodynamic responses from the central sulcus in human subjects during an event-related, simple reaction time task. Specifically, we determine the contribution of subject, day, and scanning session (within a day) to variability in the shape of evoked hemodynamic response. We find that while there is significant and substantial variability in the shape of responses collected across subjects, responses collected during multiple scans within a single subject are less variable. The results are discussed in terms of the impact of response variability upon sensitivity and specificity of analyses of event-related fMRI designs.

Adult↗
PubMed1998

An area within human ventral cortex sensitive to "building" stimuli: evidence and implications.

Isolated, ventral brain lesions in humans occasionally produce specific impairments in the ability to use landmarks, particularly buildings, for way-finding. Using functional MRI, we tested the hypothesis that there exists a cortical region specialized for the perception of buildings. Across subjects, a region straddling the right lingual sulcus was identified that possessed the functional correlates predicted for a specialized building area. A series of experiments discounted several alternative explanations for the behavior of this site. These results are discussed in terms of their impact upon our understanding of the functional structure of visual processing, disorders of topographical disorientation, and the influence of environmental conditions upon neural organization.

Adolescent↗
PubMed1998

Functional MRI studies of spatial and nonspatial working memory.

Single-unit recordings in monkeys have revealed neurons in the lateral prefrontal cortex that increase their firing during a delay between the presentation of information and its later use in behavior. Based on monkey lesion and neurophysiology studies, it has been proposed that a dorsal region of lateral prefrontal cortex is necessary for temporary storage of spatial information whereas a more ventral region is necessary for the maintenance of nonspatial information. Functional neuroimaging studies, however, have not clearly demonstrated such a division in humans. We present here an analysis of all reported human functional neuroimaging studies plotted onto a standardized brain. This analysis did not find evidence for a dorsal/ventral subdivision of prefrontal cortex depending on the type of material held in working memory, but a hemispheric organization was suggested (i.e., left-nonspatial; right-spatial). We also performed functional MRI studies in 16 normal subjects during two tasks designed to probe either nonspatial or spatial working memory, respectively. A group and subgroup analysis revealed similarly located activation in right middle frontal gyrus (Brodmann's area 46) in both spatial and nonspatial [working memory-control] subtractions. Based on another model of prefrontal organization [M. Petrides, Frontal lobes and behavior, Cur. Opin. Neurobiol., 4 (1994) 207-211], a reconsideration of the previous imaging literature data suggested that a dorsal/ventral subdivision of prefrontal cortex may depend upon the type of processing performed upon the information held in working memory.

Adult↗
PubMed1998

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Adolescent↗
PubMed1997

Empirical analyses of BOLD fMRI statistics. I. Spatially unsmoothed data collected under null-hypothesis conditions.

Temporal autocorrelation, spatial coherency, and their effects on voxel-wise parametric statistics were examined in BOLD fMRI null-hypothesis, or "noise," datasets. Seventeen normal, young subjects were scanned using BOLD fMRI while not performing any time-locked experimental behavior. Temporal autocorrelation in these datasets was described well by a 1/frequency relationship. Voxel-wise statistical analysis of these noise datasets which assumed independence (i.e., ignored temporal autocorrelation) rejected the null hypothesis at a higher rate than specified by the nominal alpha. Temporal smoothing in conjunction with the use of a modified general linear model (Worsley and Friston, 1995, NeuroImage 2: 173-182) brought the false-positive rate closer to the nominal alpha. It was also found that the noise fMRI datasets contain spatially coherent time signals. This observed spatial coherence could not be fully explained by a continuously differentiable spatial autocovariance function and was much greater for lower temporal frequencies. Its presence made voxel-wise test statistics in a given noise dataset dependent, and thus shifted their distributions to the right or left of 0. Inclusion of a "global signal" covariate in the general linear model reduced this dependence and consequently stabilized (i.e., reduced the variance of) dataset false-positive rates.

Artifacts↗
PubMed1997

Empirical analyses of BOLD fMRI statistics. II. Spatially smoothed data collected under null-hypothesis and experimental conditions.

In the companion to this paper (E. Zarahn, G. K. Aguirre, and M. D'Esposito, 1997, NeuroImage, 179-197), we describe an implementation of a general linear model for autocorrelated observations in which the voxel-wise false-positive rates in fMRI "noise" datasets were stabilized and brought close to theoretical values. Here, implementations of the model are tested for use with statistical parametric mapping analysis of spatially smoothed fMRI data. Analyses using varying models of intrinsic temporal autocorrelation and either including or excluding a global signal covariate were conducted upon human subject data collected under null hypothesis as well as under experimental conditions. We found that smoothing with an empirically derived impulse response function (IRF), combined with a model of the intrinsic temporal autocorrelation in spatially smoothed fMRI data, resulted in a map-wise false-positive rate which did not exceed a 5% level when a nominal alpha = 0.05 tabular threshold was applied. Use of other models of intrinsic temporal autocorrelation resulted in map-wise false-positive rates that significantly exceeded this level. fMRI data collected while subjects performed a behavioral task were used to examine (a) task-dependent global signal changes and (b) the dependence of sensitivity on the temporal smoothing kernel and inclusion/exclusion of a global signal covariate. The global signal changes within an fMRI dataset were shown to be influenced by the performance of a behavioral task. However, the inclusion of this measure as a covariate did not have an adverse affect upon our measure of sensitivity. Finally, use of an empirically derived estimate of the IRF of the system was shown to result in greater map-wise sensitivity for signal changes than the use of a broader (in time) Poisson (parameter = 8 s) kernel.

Adult↗
PubMed1997

A trial-based experimental design for fMRI.

An experimental design for functional MRI (fMRI) is presented whose conceptual units of analysis are behavioral trials, in contrast to blocks of trials. This type of design is referred to as a trial-based (TB) fMRI design. It is explained how TB designs can afford the ability to: (1) randomize the presentation of behavioral trials and (2) utilize intertrial variance in uncontrolled behavioral measures to examine their functional correlates. A particular type of TB design that involves modeling trial-evoked fMRI responses with one or more shifted impulse response functions is described. This design is capable of discriminating functional changes occurring during temporally separated behavioral subcomponents within trials. An example of such a design is implemented and its statistical specificity, functional sensitivity, and functional specificity are tested.

Adult↗
PubMed1997

The effect of pacing of experimental stimuli on observed functional MRI activity.

Neuroimaging activation studies typically observe signals during two or more periods of differing cognitive activity which are then analyzed by a subtraction to test for localized neuroanatomical dissociations between cognitive tasks. Significant activity found between task conditions is frequently assumed to reflect a novel cognitive process present in one task and not the other. We present a conceptual framework that considers the neural mechanisms underlying such observed neuroimaging changes. We propose that neuroimaging experiments which present stimuli at a fixed pace (where each trial takes the same amount of time) will be sensitive to changes in both duration and intensity of neural processing. In contrast, the signal observed during a self-paced design is derived from neural processing averaged over the reaction time and hence could be less sensitive to differences in duration of neural processing. As an empirical demonstration of these ideas, we studied normal subjects using echoplanar functional MRI during two visuospatial tasks (matching of either ROTATED or NONROTATED stimuli) performed using FIXED and SELF-PACED designs. In both pacing designs, reaction times were greater in the ROTATED than NONROTATED task, interpreted as a greater duration of neural processing during the ROTATED compared to the NONROTATED task. In the FIXED-PACED design, significantly greater signal was present within a parieto-occipital cortical region during the ROTATED task compared to the NONROTATED task. This difference was not observed during the SELF-PACED design. This result illustrates the importance of considering trial pacing in the interpretation of functional neuroimaging activation studies.

Adult↗
PubMed1996

Activation of the prefrontal cortex during judgments of recency: a functional MRI study.

Animal and human lesion studies have consistently shown that damage to the prefrontal lobe disrupts performance on tasks requiring memory for temporal context. In this study, functional magnetic resonance imaging (fMRI) was used to explore the brain regions associated with judgements of relative recency in healthy humans. Bilateral dorsolateral prefrontal cortex (Brodmann's area [BA] 9) was more active during a verbal recency judgment task than during a non-mnemonic control task. Activation related to temporal context recognition was also observed in midline supplementary motor area (BA 6) and left precuneus (BA 7). This study provides further evidence that memory for temporal context requires the prefrontal cortex and is the first to demonstrate this association in healthy humans. The current findings also suggest the possibility that recognition of context and recognition of episodic content may involve similar brain systems.

Adult↗