Prefrontal cortical activation associated with working memory in adults and preschool children: an event-related optical topography study

It is well known that lateral areas of the prefrontal cortex (LPFC) play a central role in working memory (a critical basis of various cognitive functions), but it remains unknown whether the LPFC of children of preschool age is responsible for working memory. To address this issue, we adopted a recently developed non-invasive imaging technique, optical topography (OT), which can potentially be applied to functional mapping in childhood. We firstly examined changes of activity in the LPFC using OT while adult subjects performed an item-recognition task, which requires working memory, under different memory-load conditions. We observed activation in the bilateral LPFC during performance of this task, the magnitude of which differed depending on memory-load. Then, we applied the same technique on 5- and 6-year-old children and observed the activation associated with working memory in the LPFC. Areas and properties of such activity were similar in adults and preschool children. Thus, for the first time, we demonstrate that the LPFC of preschoolers is active during working memory processes, indicating that in 5- and 6-year-old children, the LPFC has already developed processing of this important cognitive function.     

The neural correlates of human working memory for haptically explored object orientations

Skillful object manipulation requires that haptically explored spatial object characteristics like orientation be adequately represented in working memory. In the current functional magnetic resonance imaging study, healthy right-handed participants explored a bar-shaped reference object with the left hand, memorizing its orientation. After a variable delay (0.5, 5, or 10 s), participants used their right hand to match the orientation by rotating a second, identical object. In the first seconds of the delay, right sensorimotor cortex was active, whereas clusters in left anterior prefrontal cortex (aPFC) (Brodmann area 10) became dominant 2 s after the end of exploration, showing sustained activity for several seconds. In contrast, left parieto-occipital cortex was involved toward the end of the delay interval. Our results indicate that a dynamic network of brain areas subserves hapticospatial information processing in the delay between haptic stimulus exploration and orientation matching. We propose that haptic sensory traces, maintained in contralateral sensorimotor cortex, are transformed into more abstract hapticospatial representations in the early delay stages. Maintenance of these representations engages aPFC and parieto-occipital cortex. Whereas aPFC possibly integrates spatial and motor components of hapticospatial working memory, parieto-occipital cortex might be involved in orientation imagery, supporting working memory, and the preparation of haptic matching.     

Increased neural efficiency with repeated performance of a working memory task is information-type dependent

Unlike tasks in which practice leads to an automatic stimulus-response association, it is thought working memory (WM) tasks continue to require cognitive control processes after repeated performance. Previous studies investigating WM task repetition are in accord with this. However, it is unclear whether changes in neural activity after repetition imply alterations in general control processes common to all WM tasks or are specific to the selection, encoding and maintenance of the relevant information. In the present study, functional magnetic resonance imaging (fMRI) was used to examine changes during sample, delay and test periods during repetition of both object and spatial delayed recognition tasks. We found decreases in fMRI activation in both spatial and object-selective areas after spatial WM task repetition, independent of behavioral performance. Few areas showed changed activity after object WM task repetition. These results indicate that spatial task repetition leads to increased efficiency of maintaining task-relevant information and improved ability to filter out task-irrelevant information. The specificity of this repetition effect to the spatial task suggests a difference exists in the nature of the representation of object and spatial information and that their maintenance in WM is likely subserved by different neural systems.     

Functional connectivity of cortical networks involved in bimanual motor sequence learning

Motor skill learning requires the involvement and integration of several cortical and subcortical regions. In this study, we focus on how the functional connectivity of cortical networks changes with the acquisition of a novel motor skill. Using functional magnetic resonance imaging, we measured the localized blood oxygenation level-dependent (BOLD) signal in cortical regions while subjects performed a bimanual serial reaction time task under 2 conditions: 1) explicitly learning a novel sequence (NOVEL) and 2) playing a previously learned sequence (LEARNED). To investigate stages of learning, each condition was further divided into nonoverlapping early and late conditions. Functional connectivity was measured using a task-specific low-frequency coherence analysis of the data. We show that within the cortical motor network, the sensorimotor cortex, premotor cortex, and supplementary motor area have significantly greater inter- and intrahemispheric coupling during the early NOVEL condition compared with the late NOVEL condition. Additionally, we observed greater connectivity between frontal regions and cortical motor regions in the early versus late NOVEL contrast. No changes in functional connectivity were observed in the LEARNED condition. These results demonstrate that the functional connectivity of the cortical motor network is modulated with practice and suggest that early skill learning is mediated by enhanced interregional coupling.     

Functional brain mapping of the macaque related to spatial working memory as revealed by PET

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.     

Role of prefrontal and anterior cingulate regions in decision-making processes shared by memory and nonmemory tasks

In the episodic retrieval (ER) domain, activations in right dorsolateral prefrontal cortex (DLPFC) are often attributed to postretrieval monitoring. Yet, right DLPFC activations are also frequently found during nonmemory tasks. To investigate the role of this region across different cognitive functions, we directly compared brain activity during ER and visual perception (VP) using event-related functional magnetic resonance imaging. In the ER task, participants decided whether words were old or new, whereas in the VP task, they decided which of the two colored screen areas was larger. In both tasks, each decision was followed by a confidence rating. The main finding was that right DLPFC (Brodmann area 46/10) activity was greater for low- than for high-confidence decisions in both tasks, demonstrating a general role in decision making. Even when reaction times (RTs) were included in the model, confidence remained the significant predictor of activity, suggesting that right DLPFC is involved in discontinuous evaluation rather than in continuous monitoring. In contrast, activity in anterior cingulate cortex was not only greater for low-confidence decisions but also increased with RT, reflecting a role in continuous conflict monitoring. Overall, the results demonstrate how direct cross-function comparisons clarify the generality and specificity of the functions of various brain regions.     

Population vector analysis of primate prefrontal activity during spatial working memory

Population vectors were used to examine information represented by a population of prefrontal activity and its temporal change during spatial working memory processes while monkeys performed ODR and R-ODR tasks. In the ODR task, monkeys made a saccade to the cue location after the delay, whereas in the R-ODR task, they made a saccade 90 degrees clockwise from the cue location. We first constructed population vectors using cue- and response-period activity. The directions of population vectors were similar to the cue directions and the saccade target directions, respectively, indicating that population vectors correctly represented information regarding directions of visual cues and saccade targets. We then calculated population vectors during a 250 ms time-window from the cue presentation to the end of the response period. In the ODR task, all population vectors were directed toward the cue direction. However, in the R-ODR task, the population vector gradually rotated during the delay period from the cue direction to the saccade direction. These results indicate that spatial information represented by a population of prefrontal activity can be shown as the direction of the population vector and that its temporal change during spatial working memory tasks can be depicted as the temporal change of the vector's direction.     

Feeling the real world: limbic response to music depends on related content

Emotions are often object related--they are about someone or something in the world. It is yet an open question whether emotions and the associated perceptual contents that they refer to are processed by different parts of the brain or whether the brain regions that mediate emotions are also involved in the processing of the associated content they refer to. Using functional magnetic resonance imaging, we showed that simply combining music (rich in emotion but poor in information about the concrete world) with neutral films (poor in emotionality but rich in real-world details) yields increased activity in the amygdala, hippocampus, and lateral prefrontal regions. In contrast, emotional music on its own did not elicit a differential response in these regions. The finding that the amygdala, the heart of the emotional brain, responds increasingly to an emotional stimulus when it is associated with realistic scenes supports a fundamental role for concrete real-world content in emotional processing.     

Functional MRI of working memory in paediatric head injury

A case study examining the recovery of a 9 year old boy who sustained a severe head injury is reported. The subject sustained damage to the left parietal-occipital and right frontal-parietal regions. Structural and functional imaging and cognitive data were collected at the time of injury and 1 year post-injury. Cognitive assessment revealed improvement over time. Functional imaging at the time of injury revealed minimal activation in the right posterior temporal region. Imaging 1 year post-injury revealed increased activation in the right pre-frontal cortex, bilateral pre-motor cortex and bilateral posterior parietal cortex. This activation pattern is consistent with the performance of unaffected individuals on working memory tasks. These findings differ from those in the adult literature and suggest an alternative pattern of recovery of function in children.     

Attentional modulation of object representations in working memory

We investigated the role of object-based attention in modulating the maintenance of faces and scenes held online in working memory (WM). Participants had to remember a face and a scene, while cues presented during the delay instructed them to orient their attention to one or the other item. Event-related functional magnetic resonance imaging revealed that orienting attention in WM modulated the activity in fusiform and parahippocampal gyri, involved in maintaining representations of faces and scenes respectively. Measures from complementary behavioral studies indicated that this increase in activity corresponded to improved WM performance. The results show that directed attention can modulate maintenance of specific representations in WM, and help define the interplay between the domains of attention and WM.     

Living related liver transplantation in children with hypoxemia related to intrapulmonary shunting

Abstract  Living related liver transplantation (LRLT) was performed in seven children with hypoxemia related to intrapulmonary shunting. Based on the degree of the shunt ratio calculated by technetium ⁹⁹m macroaggregated albumin (MAA) scintigraphy, the seven patients were classified in the moderate (shunt ratio under 40 %, n = 4) or severe group (shunt ratio over 40 %, n = 3). While Pa was maintained over 60 mmHg in the moderate group, that in the severe group continued at a low level of under 40 mmHg in the early postoperative period. However, 48 h after surgery the arterial ketone body ratio recovered to a safe level of 1.0 in both groups. Values of aspartate aminotransferase and serum total bilirubin decreased at a constant rate in both groups. Six patients survived, but one died of portal vein thrombosis on the 53 rd postoperative day. Five of six surviving patients recovered from hypoxemia. We concluded that the transplanted liver can tolerate the stress of severe hypoxemia after LRLT.     

Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans

Ventromedial prefrontal cortex (VMF) damage can lead to impaired decision-making. This has been studied most intensively with the Iowa gambling task (IGT), a card game that asks subjects to overcome an initial attraction to high-payoff decks as losses begin to accrue. VMF subjects choose from the high risk decks more often than controls, but the fundamental impairments driving poor performance on this complex task have yet to be established. There is also conflicting evidence regarding the role of the dorsolateral prefrontal cortex (DLF) in this task. The present study examined whether poor performance on the IGT was specific for VMF damage and whether fundamental impairments in reversal learning contributed to IGT performance. We found that both VMF and DLF damage leads to impaired IGT performance. The impairment of VMF subjects, but not of DLF subjects, seems to be largely explained by an underlying reversal learning deficit.     

Differential contributions of prefrontal, medial temporal, and sensory-perceptual regions to true and false memory formation

The neural correlates of true memory formation (TMF) and false memory formation (FMF) were investigated using functional magnetic resonance imaging (fMRI). Using a parametric subsequent memory paradigm, encoding activity was analyzed as a function of whether it predicted subsequent hits to targets (TMF activity) or subsequent false alarms to critical lures (FMF activity). The fMRI analyses yielded 3 main findings. First, the left prefrontal cortex (PFC) was involved in both TMF and FMF activities. This finding is consistent with the evidence that semantic elaboration, which has been associated with left PFC, tends to enhance both true and false remembering. Second, the left posterior medial temporal lobes (MTLs) contributed to TMF but not to FMF activity. This finding is consistent with the notion that MTL is involved in the storage of a consciously, but not unconsciously, processed event. Third, late visual regions were engaged in both TMF and FMF activities, whereas early visual areas were involved primarily in TMF activity. This dissociation indicates that elaborative perceptual processing, but not basic sensory processing, contributes to false remembering. Taken together, the results suggest that FMF is an unintended consequence, or by-product, of elaborative semantic and visual encoding processes.     

Nonvisual codes and nonvisual brain areas support visual working memory

Systems models hold working memory to depend on specialized, domain-specific storage buffers. Here, however, we demonstrate that short-term retention of the identity or location of visually presented stimuli is disrupted by nonvisual secondary tasks performed in the dark-passive listening to nouns or endogenous generation of saccades, respectively. This indicates that the short-term retention of visual information relies on multiple mental codes, some of them nonvisual. Event-related functional magnetic resonance imaging (fMRI) reveals the neural correlates of these interference effects to be more complex and more regionally specific than previously described. Although nonspecific dual-task effects produce a generalized decrease of task-evoked fMRI response across many brain regions, the interference-specific effect is a relative increase of activity localized to regions associated with the secondary task in question: left hemisphere perisylvian cortex in the case of passive listening distraction and frontal oculomotor regions in the case of saccadic distraction. Within these regions, the neural interference effects are specific to voxels that show delay-period activity on unfilled memory trials. They also predict individual differences in the magnitude of the behavioral interference effect. These results indicate that nonvisual processes supported by nonvisual brain areas contribute importantly to "visual" working memory performance.     

Neural system for controlling the contents of object working memory in humans

Working memory (WM), the active maintenance of currently relevant information, is a flexible system allowing for fast and frequent goal-directed changes of rehearsed information. Successful WM maintenance prevents interference from distracting stimuli while allowing new task-relevant information to update the contents of WM. We used functional magnetic resonance imaging to show that when WM contents were updated, regardless of stimulus type (faces or houses), a frontoparietal network showed transient increases in activation. Some of these regions are highly similar to those identified in studies of shifting attention, supporting the idea that updating WM involves a change in the attentional priority afforded to the current perceptual input. A region within the mid-ventrolateral prefrontal cortex, near the junction of the inferior frontal sulcus and precentral sulcus (inferior frontal junction), that has previously been implicated in cognitive control, demonstrated transient increases in activity during updating as well as sustained maintenance activity. A more anterior prefrontal region, middle frontal gyrus, previously implicated in protecting the contents of WM from interfering stimuli during maintenance, demonstrated transient increases in activity during updating. The current study suggests that updating WM results from a combination of increased attention to the visual stimulus and a change in the system's interference protection state.     

Positive evidence against human hippocampal involvement in working memory maintenance of familiar stimuli

Subjects (n = 40) performed a delayed item recognition task for visually presented letters with three set sizes (1, 3 or 6 letters). Accuracy was close to ceiling at all set sizes, so we took set size as a proxy for WM load (i.e. the amount of information being maintained in WM). Functional magnetic resonance imaging (fMRI) signal associated with the delay period increased in a nearly linear fashion with WM load in the left inferior frontal gyrus/anterior insula (possibly Broca's area, BA 44/45), right anterior insula, bilateral caudate, bilateral precentral gyrus (BA 6), bilateral middle frontal gyrus (BA 9/46), bilateral inferior parietal lobule (with foci in both BA 39 and 40), left superior parietal lobule (BA 7), medial frontal gyrus (BA 6), anterior cingulate gyrus (BA 32) and bilateral superior frontal gyrus (BA 8). These results lend support to the idea that at least some of the cortical mechanisms of WM maintenance, potentially rehearsal, exhibit a scaling with WM load. In contrast, the delay-related fMRI signal in hippocampus followed an inverted U-shape, being greatest during the intermediate level of WM load, with relatively lower values at the lowest and highest levels of WM load. This pattern of delay-related fMRI activity, orthogonal to WM load, is seemingly not consonant with a role for hippocampus in WM maintenance of phonologically codable stimuli. This finding could possibly be related more to the general familiarity of the letter stimuli than their phonological codability per se.     

Neural correlates of change detection and change blindness in a working memory task

Detecting changes in an ever-changing environment is highly advantageous, and this ability may be critical for survival. In the present study, we investigated the neural substrates of change detection in the context of a visual working memory task. Subjects maintained a sample visual stimulus in short-term memory for 6 s, and were asked to indicate whether a subsequent, test stimulus matched or did not match the original sample. To study change detection largely uncontaminated by attentional state, we compared correct change and correct no-change trials at test. Our results revealed that correctly detecting a change was associated with activation of a network comprising parietal and frontal brain regions, as well as activation of the pulvinar, cerebellum, and inferior temporal gyrus. Moreover, incorrectly reporting a change when none occurred led to a very similar pattern of activations. Finally, few regions were differentially activated by trials in which a change occurred but subjects failed to detect it (change blindness). Thus, brain activation was correlated with a subject's report of a change, instead of correlated with the physical change per se. We propose that frontal and parietal regions, possibly assisted by the cerebellum and the pulvinar, might be involved in controlling the deployment of attention to the location of a change, thereby allowing further processing of the visual stimulus. Visual processing areas, such as the inferior temporal gyrus, may be the recipients of top-down feedback from fronto-parietal regions that control the reactive deployment of attention, and thus exhibit increased activation when a change is reported (irrespective of whether it occurred or not). Whereas reporting that a change occurred, be it correctly or incorrectly, was associated with strong activation in fronto-parietal sites, change blindness appears to involve very limited territories.     

Kinesthetic working memory and action control within the dorsal stream

There is wide agreement that the "dorsal (action) stream" processes visual information for movement control. However, movements depend not only on vision but also on tactile and kinesthetic information (=haptics). Using functional magnetic resonance imaging, the present study investigates to what extent networks within the dorsal stream are also utilized for kinesthetic action control and whether they are also involved in kinesthetic working memory. Fourteen blindfolded participants performed a delayed-recognition task in which right-handed movements had to be encoded, maintained, and later recognized without any visual feedback. Encoding of hand movements activated somatosensory areas, superior parietal lobe (dorsodorsal stream), anterior intraparietal sulcus (aIPS) and adjoining areas (ventrodorsal stream), premotor cortex, and occipitotemporal cortex (ventral stream). Short-term maintenance of kinesthetic information elicited load-dependent activity in the aIPS and adjacent anterior portion of the superior parietal lobe (ventrodorsal stream) of the left hemisphere. We propose that the action representation system of the dorsodorsal and ventrodorsal stream is utilized not only for visual but also for kinesthetic action control. Moreover, the present findings demonstrate that networks within the ventrodorsal stream, in particular the left aIPS and closely adjacent areas, are also engaged in working memory maintenance of kinesthetic information.     

Segmental living related small bowel transplantation in adults

The advent of small bowel transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small bowel transplantation (LR-SBTx) has been developed. Three patients with short bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmentai ileal graft from a living donor can provide complete rehabilitation for patients with short bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric bowel transplantation. Further clinical application of this procedure is warranted. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

Dynamics of prefrontal and cingulate activity during a reward-based logical deduction task

We used behavioral and functional magnetic resonance imaging (fMRI) methods to probe the cerebral organization of a simple logical deduction process. Subjects were engaged in a motor trial-and-error learning task, in which they had to infer the identity of an unknown 4-key code. The design of the task allowed subjects to base their inferences not only on the feedback they received but also on the internal deductions that it afforded (autoevaluation). fMRI analysis revealed a large bilateral parietal, prefrontal, cingulate, and striatal network that activated suddenly during search periods and collapsed during ensuing periods of sequence repetition. Fine-grained analyses of the temporal dynamics of this search network indicated that it operates according to near-optimal rules that include 1) computation of the difference between expected and obtained rewards and 2) anticipatory deductions that predate the actual reception of positive reward. In summary, the dynamics of effortful mental deduction can be tracked with fMRI and relate to a distributed network engaging prefrontal cortex and its interconnected cortical and subcortical regions.