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ABSTRACT: Working memory is an important cognitive process dependent on a network of prefrontal and posterior cortical regions. In this study we tested the effects of the mixed D1-D2 dopamine receptor agonist pergolide on component processes of human working memory using functional magnetic resonance imaging (fMRI). An event-related trial design allowed separation of the effects on encoding, maintenance, and retrieval processes. Subjects were tested with spatial and object memoranda to investigate modality-specific effects of dopaminergic stimulation. We also measured baseline working memory capacity as previous studies have shown that effects of dopamine agonists vary with working memory span. Pergolide improved reaction time for high-span subjects and impaired reaction time for low-span subjects. This span-dependent change in behavior was accompanied by span-dependent changes in delay-related activity in the premotor cortex. We also found evidence for modality-specific effects of pergolide only during the response period. Pergolide increased activity for spatial memoranda and decreased activity for object memoranda in task-related regions including the prefrontal and parietal cortices.
Neuroscience 05/2006; 139(1):359-71. · 3.38 Impact Factor
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ABSTRACT: Rehearsal in human spatial working memory is accomplished, in part, via covert shifts of spatial selective attention to memorized locations ("attention-based rehearsal"). We addressed two outstanding questions about attention-based rehearsal: the topography of the attention-based rehearsal effect, and the mechanism by which it operates. Using event-related fMRI and a procedure that randomized the presentation of trials with delay epochs that were either filled with a flickering checkerboard or unfilled, we localized the effect to extrastriate areas 18 and 19, and confirmed its absence in striate cortex. Delay-epoch activity in these extrastriate regions, as well as in superior parietal lobule and intraparietal sulcus, was also lateralized on unfilled trials, suggesting that attention-based rehearsal produces a baseline shift in areas representing the to-be-remembered location in space. No frontal regions (including frontal eye fields) demonstrated lateralized activity consistent with a role in attention-based rehearsal.
Cognitive Brain Research 08/2004; 20(2):194-205. · 3.77 Impact Factor
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ABSTRACT: Anatomic structures have been linked to the mnemonic component of working memory, but the neural network underlying associated decision processes remains elusive. Here we present an event-related functional magnetic resonance imaging study that measured activity during the decision period of a delayed face recognition task. A double dissociation of activity between anterior cingulate cortex (ACC), and a network including left fusiform face area (FFA) and left dorsolateral prefrontal cortex (DLPFC), reflected whether a probe face matched the remembered face at the time of decision. Greater activity in the left FFA and left DLPFC correlated with probe faces that matched the remembered face; in contrast, activity in ACC was greater when the probe face did not match the remembered face. These results support a model where frontal regions act in concert with stimulus-specific temporal structures to make recognition decisions about visual stimuli.
Neuron 01/2002; 32(5):947-55. · 14.74 Impact Factor
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ABSTRACT: Using event-related functional magnetic resonance imaging, we investigated the role of medial temporal regions during active maintenance of information over short delays or working memory. In experiment 1, we observed sustained bilateral hippocampal activation during maintenance of novel faces across a short delay period but not during face encoding or recognition. In contrast, we observed transient right parahippocampal activation during encoding and recognition but not during maintenance. We replicated these findings in experiment 2 and further determined that anterior hippocampal activation was greater during maintenance of novel than familiar faces. Our results reveal the importance of medial temporal lobe regions for the active maintenance of novel information in the absence of perceptual stimulation.
Neuron 10/2001; 31(5):865-73. · 14.74 Impact Factor
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ABSTRACT: Studies of human subjects performing cognitive tasks on and off dopaminergic drugs have suggested a specific role of dopamine in cognitive processes, particularly in working memory and prefrontal "executive" functions. However, the cortical effects of these drugs have been poorly understood. We used functional magnetic resonance imaging (fMRI) to examine both task-specific and general changes in cortical activity associated with bromocriptine, a selective agonist for D-2 dopamine receptors. Bromocriptine resulted in task-specific modulations of task-related activity in three cognitive tasks. Across tasks, the overall effect of the drug was to reduce task-related activity. We also observed drug effects on behavior that correlated with individual differences in memory span. We argue that bromocriptine may show both task-specific modulation and task-general inhibition of neural activity due to dopaminergic neurotransmission.
Human Brain Mapping 05/2001; 12(4):246-57. · 5.88 Impact Factor
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ABSTRACT: Updating refers to (1) discarding items from, (2) repositioning items in, and (3) adding items to a running working memory span. Our behavioral and fMRI experiments varied three factors: trial length, proactive interference (PI), and group integrity. Group integrity reflected whether the grouping of items at the encoding stage was violated at discarding. Behavioral results were consistent with the idea that updating processes have a relatively short refractory period and may not fatigue, and they revealed that episodic information about group context is encoded automatically in working memory stimulus representations. The fMRI results did not show evidence that updating requirements in a task recruit executive control processes other than those supporting performance on nonupdating trials. They did reveal an item-accumulation effect, in which signal increased monotonically with the number of items presented during the trial, despite the insensitivity of behavioral measures to this factor. Behavioral and fMRI correlates of PI extended previous results and rejected an alternative explanation of PI effects in working memory.
Cognitive Affective & Behavioral Neuroscience 04/2001; 1(1):10-21. · 3.57 Impact Factor
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ABSTRACT: Previous fMRI results suggest that extrastriate visual areas have a predominant role in perceptual processing while the prefrontal cortex (PFC) has a predominant role in working memory. In contrast, single-unit recording studies in monkeys have demonstrated a relationship between extrastriate visual areas and visual working memory tasks. In this study we tested whether activity in both the PFC and fusiform face area (FFA) changed with increasing demands of an n-back task for gray-scale faces. Since stimulus presentation was identical across conditions, the n-back task allowed us to parametrically vary working memory demands across conditions while holding perceptual and motor demands constant. This study replicated the result of PFC areas of activation that increased directly with load n of the task. The novel finding in all subjects was FFA activation that also increased directly with load n of the task. Since perceptual demands were equivalent across the three task conditions, these findings suggest that activity in both the PFC and the FFA vary with face working memory demands.
Cognitive Brain Research 02/2001; 10(3):355-64. · 3.77 Impact Factor
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ABSTRACT: Cognitive theory posits association by juxtaposition or by fusion. We employed the measurement of event-related brain potentials (ERPs) to a concept fusion task in order to explore memory encoding of these two types of associations between word pairs, followed by a memory test for original pair order. Encoding processes were isolated by subtracting fusion task ERPs corresponding to pairs later retrieved quickly from ERPs corresponding to pairs later retrieved slowly, separately for pairs fused successfully and unsuccessfully (i.e., juxtaposed). Analyses revealed that the encoding of these two types of associations yields different ERP voltage polarities, scalp topographies, and brain sources extending over the entire time course of processing.
Neuron 02/2001; 29(1):297-306. · 14.74 Impact Factor
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ABSTRACT: Results from neuroimaging studies have led to competing theories regarding the contributions of prefrontal regions to memory formation and retrieval. To investigate this issue, we used event-related functional magnetic resonance imaging to assess prefrontal activation during encoding and retrieval of pictures of objects. Responses to studied and unstudied objects at retrieval were compared between two tests with differing demands for the specificity of information to be retrieved (source vs old-new recognition). Results showed that bilateral ventral [Brodmann's areas (BA) 44, 45, and 47] and right dorsal (BA 9) prefrontal regions were activated during both encoding and retrieval, but activity in these regions was not reliably modulated by the specificity of information to be retrieved. A region in left anterior prefrontal cortex (BA 10/46) was reliably activated during retrieval trials, and activation in this region increased with demands to retrieve perceptually detailed information about studied objects. Our results show that left anterior prefrontal cortex is engaged during the monitoring and evaluation of specific memory characteristics at retrieval-a process critical for accurate episodic remembering.
Journal of Neuroscience 12/2000; 20(22):RC108. · 7.11 Impact Factor
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ABSTRACT: Task-switching paradigms, in which subjects are typically asked to switch between different S-R mappings, can be considered operationalizations of executive control. Such paradigms are therefore potentially useful in investigating the neural bases of control functions. Here, we present the results of an fMRI study intended to examine two separable components of task-switching: preparation, and the residual shift cost identified by Rogers and Monsell [13]. In analyses restricted to functionally identified regions of interest, we found robust evidence of greater activity for switch trials, compared to repeat trials. This pattern was present both at the time of stimulus presentation and prior to the switch trial. In analyses of the entire brain, we were able to identify one area in the superior parietal lobule that was active during switching but was not part of the apparent network of task-related regions. We conclude that switch trials are neurally distinct from repeat trials in eliciting generally greater neural activity both before and during the performance of a trial.
Cognitive Brain Research 10/2000; 10(1-2):189-96. · 3.77 Impact Factor
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ABSTRACT: Working memory refers to the short-term retention of information that is no longer accessible in the environment, and the manipulation of this information, for subsequent use in guiding behavior. In this review, we will present data from a series of event-related functional magnetic-resonance-imaging (fMRI) studies of delayed-response tasks that were designed to investigate the role of different regions of the prefrontal cortex (PFC) during different working-memory component processes. From these data, we conclude that: (1) lateral PFC is anatomically organized according to the types of cognitive operations that one performs when attempting to temporarily maintain and manipulate information; and (2) consistent with the picture that has emerged from the monkey electrophysiological literature, human lateral PFC is involved in several encoding- and response-related processes as well as mnemonic and nonmnemonic processes that are engaged during the temporary maintenance of information. Thus, lateral PFC activity cannot be ascribed to the function of a single, unitary cognitive operation.
Experimental Brain Research 08/2000; 133(1):3-11. · 2.39 Impact Factor
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ABSTRACT: Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.
Nature Neuroscience 06/2000; 3(5):509-15. · 15.53 Impact Factor
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ABSTRACT: Delayed-response tasks are behavioral paradigms in which subjects must remember stimulus attributes across a delay to subsequently perform the appropriate motor response. Quintana and Fuster (1992), reported that there exist subpopulations of neurons in monkey lateral prefrontal cortex (PFC) whose firing rates during the delay are tuned to either sensorial attributes of the stimulus (i.e., involved in sensory memory) or the direction of a postdelay motor response associated with the stimulus (i.e., involved in motor preparation). We studied human subjects with an event-related fMRI method that would allow us to test the hypothesis that there are regions within the PFC that are recruited during both motor preparation and sensory memory. Subjects performed a delayed-response task with two types of trials that either (1) allowed subjects to prepare during a delay period for a specific motor response or (2) required that subjects maintain a sensory attribute (specifically, color) during a delay period for correct performance postdelay. It was assumed that during the delay periods, the delayed-response trials would engage motor preparation while delayed-match trials would engage sensory memory. Behavioral data supported this assumption. Imaging results support the hypothesis that the PFC is involved in both motor preparation and sensory memory. Furthermore, no selectivity (in terms of intensity of neural representation on the spatial scale of the voxel size <5 mm(3)) for motor preparation over sensory memory (or vice-versa) was detected within the PFC. This latter result fails to support a gross anatomical segregation within the PFC with respect to involvement in these two cognitive processes.
NeuroImage 05/2000; 11(5 Pt 1):400-8. · 5.89 Impact Factor
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ABSTRACT: Event-related experimental design and analysis techniques for functional magnetic resonance imaging (fMRI) take advantage of the intrinsic temporal resolution of fMRI to permit investigation of complex human behaviors on the time scale over which they can occur. The protocol described in this report permits the effective isolation and assessment of variance in the fMRI signal that is attributable solely to the delay portion of delayed-response tasks. It permits, therefore, evaluation of the purely mnemonic portions of working memory tasks without requiring the "cognitive subtraction" of nonmnemonic components of such tasks, such as visual processing and motor output. Features of this event-related fMRI technique include the empirical derivation of an impulse response function (IRF) from each subject participating in the experiment, single-subject and random effects group analyses, use of t-values of dependent measures, and the use of regions of interest (ROI) to improve the sensitivity of a priori contrasts. This report provides a detailed exposition of the research methodology of our event-related fMRI technique, the rationale behind many of its critical features, and examples of its application to two empirical datasets.
Brain Research Protocols 03/2000; 5(1):57-66. · 1.82 Impact Factor
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ABSTRACT: Changes in neuronal firing rates during periods of time when subjects are required to remember information (retention delays) have been reported in non-human primates. In humans, tests for such functional changes using hemodynamic markers of neural activity have typically relied on cognitive subtraction. However, the temporal resolution of fMRI allows a more direct test than that afforded by cognitive subtraction of the idea that certain brain regions may increase their neural activity during retention delays in humans. Using a method that exploits this temporal resolution, increased functional activity attributable to a retention delay for spatial information in regions proximate to/within the right frontal eye field and the right superior parietal lobule were detected (in four out of four and three out of four subjects, respectively; this is an internal replication of the results of [E. Zarahn, G.K. Aguirre, M. D'Esposito, Temporal isolation of the neural correlates of spatial mnemonic processing with fMRI, Cognit. Brain Res., 7 (1999) 255-268. ]). Second, a model in which ventral and not dorsal prefrontal cortex in humans is involved in simply maintaining spatial information was tested. The results disputed this model as increases in fMRI signal attributable to the retention delay were detected more frequently in dorsal than ventral prefrontal cortex. Third, a model which posited that the intensity of neural activity is causally related to the accuracy of spatial mnemonic representation was tested by comparing retention delay signal between correct and incorrect trials. The results did not support this model in any of the regions tested.
Cognitive Brain Research 02/2000; 9(1):1-17. · 3.77 Impact Factor
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ABSTRACT: We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).
Journal of Cognitive Neuroscience 02/2000; 12 Suppl 2:2-14. · 5.18 Impact Factor
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ABSTRACT: Stroke is a leading cause of morbidity and mortality in individuals. Many patients have good functional recovery after stroke. The mechanisms of recovery remain largely unknown. Neuroimaging of patients recovering from stroke may provide important insight into the mechanisms of recovery as well as assist in the development of new rehabilitation techniques. The first part of this article reviews previous neuroimaging studies that have monitored the reorganization within the motor and language areas after stroke. In the second section, a unifying theory based on John Hughlings Jackson's "Principles of Compensation" is presented as a possible theory for recovery of function. In the final portion of the article, possible implications and future applications of neuroimaging studies for rehabilitation are presented.
Neurorehabilitation and neural repair 02/2000; 14(3):171-9. · 4.49 Impact Factor
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ABSTRACT: Behavioral studies indicate that spatial and object working memory are computed by dissociable subsystems. We investigated the neural bases of this dissociation with a whole-brain fMRI design and analysis technique that permitted direct assessment of delay-period activity, uncontaminated by other components of the trial. The task employed a "what"-then-"where" design, with an object and a spatial delay period incorporated in each trial; within-trial order of delay conditions was balanced across each scan. Our experiment failed to find evidence, at the single-subject level and at the group level, for anatomical segregation of spatial and object working memory function in the frontal cortex. Delay-period activity in the caudate nucleus revealed a sensitivity to position in the trial in the spatial, but not the object, condition. In posterior regions, spatial delay-period activity was associated with preferential recruitment of extrastriate areas falling within Brodmann's area 19 and, less reliably, the superior parietal lobule. Object-specific delay-period activity was found predominantly in ventral regions of the posterior cortex and demonstrated more topographic variability across subjects than did spatial working memory activity.
Journal of Cognitive Neuroscience 12/1999; 11(6):585-97. · 5.18 Impact Factor
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ABSTRACT: We used event-related functional MRI to investigate the neural bases of two categories of mental processes believed to contribute to performance of an alphabetization working memory task: memory storage and memory manipulation. Our delayed-response tasks required memory for the identity and position-in-the-display of items in two- or five-letter memory sets (to identify load-sensitive regions) or memory for the identity and relative position-in-the-alphabet of items in five-letter memory sets (to identify manipulation-sensitive regions). Results revealed voxels in the left perisylvian cortex of five of five subjects showing load sensitivity (as contrasted with alphabetization-sensitive voxels in this region in only one subject) and voxels of dorsolateral prefrontal cortex in all subjects showing alphabetization sensitivity (as contrasted with load-sensitive voxels in this region in two subjects). This double dissociation was reliable at the group level. These data are consistent with the hypothesis that the nonmnemonic executive control processes that can contribute to working memory function are primarily prefrontal cortex-mediated whereas mnemonic processes necessary for working memory storage are primarily posteriorly mediated. More broadly, they support the view that working memory is a faculty that arises from the coordinated interaction of computationally and neuroanatomically dissociable processes.
Proceedings of the National Academy of Sciences 11/1999; 96(22):12959-64. · 9.68 Impact Factor
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ABSTRACT: One model of the functional organization of lateral prefrontal cortex (PFC) in primates posits that this region is organized in a dorsal/ventral fashion subserving spatial and object working memory, respectively. Alternatively, it has been proposed that a dorsal/ventral subdivision of lateral PFC instead reflects the type of processing performed upon information held in working memory. We tested this hypothesis using an event-related fMRI method that can discriminate among functional changes occurring during temporally separated behavioral subcomponents of a single trial. Subjects performed a delayed-response task with two types of trials in which they were required to: (1) retain a sequence of letters across the delay period (maintenance) or (2) reorder the sequence into alphabetical order across the delay period (manipulation). In each subject, activity during the delay period was found in both dorsolateral and ventrolateral PFC in both types of trials. However, dorsolateral PFC activity was greater in manipulation trials. These findings are consistent with the processing model of the functional organization of working memory in PFC.
Brain and Cognition 11/1999; 41(1):66-86. · 3.17 Impact Factor
