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.     

A common prefrontal-parietal network for mnemonic and mathematical recoding strategies within working memory

Previous studies have indicated that the lateral prefrontal cortex (LPFC) is closely involved in strategic recoding, even when such processes lessen task demands. For example, 2 studies presented, in the spatial and verbal domains, sequences of stimuli for participants to retain during a short interval and then retrieve. Stimuli were either randomly arranged or structured (forming symmetries and regular shapes for the spatial task and mathematical patterns for the verbal task). Although participants performed the structured tasks better by reorganizing or "chunking" them into more efficient forms, LPFC activity was greater for the structured compared with the random sequences. However, although these results demonstrate that LPFC is involved in strategic recoding, regardless of the type of modality, it remains to be seen whether such a result generalizes to different types of strategic recoding processes. To test this, we presented digit sequence trials that separately emphasized mnemonic or mathematical recoding strategies. While participants were able to gain a performance benefit from either type of recoding strategy, increased LPFC activity was observed for both mathematical and mnemonic recoding trials, compared with either unstructured sequences or control conditions matched for mathematical or mnemonic processes. However, mathematically structured trials activated the LPFC significantly more than mnemonic recoding trials. In addition, lateral posterior parietal cortex was consistently coactivated with LPFC for strategic recoding trials, both in the current experiments and in previous related studies. We conclude that a prefrontal-parietal network is involved in strategic recoding in working memory, regardless of the type of recoding process.     

Separable neural bases for subprocesses of recognition in working memory

Working memory supports the recognition of objects in the environment. Memory models have postulated that recognition relies on 2 processes: assessing the degree of similarity between an external stimulus and memory representations and testing the resulting summed-similarity value against a critical level for recognition. Here, we varied the similarity between samples held in working memory and a probe to investigate these 2 processes with magnetoencephalography. Two separable components matched our expectations: First, from 280 ms after probe onset, clearly nonmatching probes differed from both similar nonmatches and matches over left frontal cortex. At 350-400 ms, these signals evolved into a pattern of gradually increasing activation as a function of sample-probe similarity, as expected for a neural representation of summed similarity. Second, a signal potentially reflecting criterion testing was observed at 600-700 ms at right frontotemporal sensors that differentiated between matches and nonmatches without further differences between similar and dissimilar probes. Thus, analysis of the time course of recognition provided strong evidence that similarity summation and criterion testing have separable neural bases. As probably both working and long-term memory recognition draw on these processes, they may be involved in many domains of behavior.     

Surgical simulation tasks challenge visual working memory and visual-spatial ability differently

Background  

New strategies for selection and training of physicians are emerging. Previous studies have demonstrated a correlation between visual-spatial ability and visual working memory with surgical simulator performance. The aim of this study was to perform a detailed analysis on how these abilities are associated with metrics in simulator performance with different task content. The hypothesis is that the importance of visual-spatial ability and visual working memory varies with different task contents.     

Persistent discharges in the prefrontal cortex of monkeys naive to working memory tasks

Neurons in the prefrontal cortex and a network of interconnected brain areas discharge in a persistent fashion after the offset of sensory stimulation. Such persistent discharges are thought to constitute a neuronal correlate of working memory. The information content of neuronal discharges and its anatomical localization across the surface of the prefrontal cortex has been a matter of debate. Discrepant results by different laboratories may be due to the effects of different training regiments and tasks used in memory tasks. In order to address how training in a memory task alters neuronal responses, we performed recordings in monkeys that were never trained in memory tasks, but passively viewed visual stimuli. We have found that a population of prefrontal neurons responded to visual stimuli and also exhibited significantly elevated responses during "delay" intervals of the task. For a population of these neurons, persistent discharges were selective for the location and feature of the preceding stimulus. These discharges were typically disrupted by the appearance of a subsequent stimulus. Our results suggest that some prefrontal neurons represent the location and identity of visual stimuli in a persistent fashion, even when the latter are not behaviorally important or required to be kept in memory.     

Dissociating neural correlates of cognitive components in mental calculation

Mental calculation is a complex cognitive operation that is composed of a set of distinct functional processes. Using functional magnetic resonance imaging (fMRI), we mapped brain activity in healthy subjects performing arithmetical tasks and control tasks evoking a comparable load on visuo-constructive, linguistic, attentional and mnemonic functions. During calculation, as well as non-mathematical tasks, similar cortical networks consisting of bilateral prefrontal, premotor and parietal regions were activated, suggesting that most of these cortical areas do not exclusively represent modules for calculation but support more general cognitive operations that are instrumental but not specific to mental arithmetic. Significant differences between calculation and the non-mathematical tasks were found in parietal sub-regions, where non-arithmetic number or letter substitution tasks preferentially activated the superior parietal lobules whereas calculation predominantly elicited activation of the left dorsal angular gyrus and the medial parietal cortices. We interpret the latter activations to reflect sub-processes of mental calculation that are related to the processing of numerical representations during exact calculation and to arithmetical fact retrieval. Finally, we found that more complex calculation tasks involving the application of calculation rules increased activity in left inferior frontal areas that are known to subserve linguistic and working memory functions. Taken together, these findings help to embed the specific cognitive operation of calculation into a neural framework that provides the required set of instrumental components. This result may further inform the cognitive modeling of calculation and adds to the understanding of neuropsychological deficit patterns in patients.     

Concurrent performance of two working memory tasks: potential mechanisms of interference

When two tasks are performed simultaneously, performance often deteriorates, with concomitant increases in reaction time and error rate. Three potential neurophysiological mechanisms behind this deterioration in performance have been considered here: (i) dual-task performance requires additional cognitive operations and activation of cortical areas in addition to those active during single-task performance; (ii) two tasks interfere if they require activation of the same part of cortex; and (iii) cross-modal inhibition causes interference between two tasks involving stimuli from different sensory modalities. Positron emission tomography was used to measure regional cerebral blood flow (rCBF) during performance of an auditory working memory (WM) task, a visual WM task, both WM tasks (dual task) and a control condition. Compared to the control condition, the auditory and visual WM tasks activated sensory-specific areas in the superior temporal gyrus and occipital pole respectively. Both WM tasks also activated overlapping parts of cortex in the dorsolateral prefrontal, inferior parietal and cingulate cortex. There was no separate cortical area which was activated only in the dual task, and thus no area which could be associated with any dual task specific cognitive process such as task-coordination or divided attention. Decrease in rCBF in one WM task did not overlap with the areas of rCBF increase in the other WM task. However, an inhibitory mechanism could not be ruled out, since the rCBF increase in sensory specific areas was smaller in the dual- task condition than in the single-task conditions. The cortical activity underlying WM was to a large extent organized in a non-sensory specific, or non-parallel, way, and the results are consistent with the hypothesis that concurrent tasks interfere with each other if they demand activation of the same part of cortex.      

Distinct neural circuits support transient and sustained processes in prospective memory and working memory

Current theories are divided as to whether prospective memory (PM) involves primarily sustained processes such as strategic monitoring, or transient processes such as the retrieval of intentions from memory when a relevant cue is encountered. The current study examined the neural correlates of PM using a functional magnetic resonance imaging design that allows for the decomposition of brain activity into sustained and transient components. Performance of the PM task was primarily associated with sustained responses in a network including anterior prefrontal cortex (lateral Brodmann area 10), and these responses were dissociable from sustained responses associated with active maintenance in working memory. Additionally, the sustained responses in anterior prefrontal cortex correlated with faster response times for prospective responses. Prospective cues also elicited selective transient activity in a region of interest along the right middle temporal gyrus. The results support the conclusion that both sustained and transient processes contribute to efficient PM and provide novel constraints on the functional role of anterior PFC in higher-order cognition.     

Volumetric correlates of spatiotemporal working and recognition memory impairment in aged rhesus monkeys

Spatiotemporal and recognition memory are affected by aging in humans and macaque monkeys. To investigate whether these deficits are coupled with atrophy of memory-related brain regions, T(1)-weighted magnetic resonance images were acquired and volumes of the cerebrum, ventricles, prefrontal cortex (PFC), calcarine cortex, hippocampus, and striatum were quantified in young and aged rhesus monkeys. Subjects were tested on a spatiotemporal memory procedure (delayed response [DR]) that requires the integrity of the PFC and a medial temporal lobe-dependent recognition memory task (delayed nonmatching to sample [DNMS]). Region of interest analyses revealed that age inversely correlated with striatal, dorsolateral prefrontal cortex (dlPFC), and anterior cingulate cortex volumes. Hippocampal volume predicted acquisition of the DR task. Striatal volume correlated with DNMS acquisition, whereas total prefrontal gray matter, prefrontal white matter, and dlPFC volumes each predicted DNMS accuracy. A regional covariance analysis revealed that age-related volumetric changes could be captured in a distributed network that was coupled with declining performance across delays on the DNMS task. This volumetric analysis adds to growing evidence that cognitive aging in primates arises from region-specific morphometric alterations distributed across multiple memory-related brain systems, including subdivisions of the PFC.     

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.     

The relationship between aging, performance, and the neural correlates of successful memory encoding

The present functional magnetic resonance imaging (fMRI) study investigated whether age-related differences in the neural correlates of successful memory encoding are modulated by memory performance. Young (mean age 22 years; N = 16) and older (mean age 69 years; N = 32) subjects were scanned while making animacy decisions on visually presented words. Memory for the words was later assessed in a recognition test, allowing fMRI activity elicited by study words to be contrasted according to subsequent memory performance. Young and older adults exhibited equivalent subsequent memory effects (enhanced activity for later remembered items) in an extensive network that included left inferior prefrontal cortex and anterior hippocampus. In posterior cingulate cortex, reversed subsequent memory effects (greater activity for later forgotten items) were of greater magnitude in young subjects. A voxel-of-interest analysis conducted on left and right prefrontal subsequent memory effects revealed that the effects were distributed more bilaterally in older than in young subjects, replicating previous findings. This age-related difference was confined to older subjects with relatively poor recognition performance, who were also the only group to demonstrate statistically significant right prefrontal subsequent memory effects. The findings suggest that relative preservation of memory performance with increasing age does not depend upon right prefrontal "over-recruitment."     

Timing and neural encoding of somatosensory parametric working memory in macaque prefrontal cortex

We trained monkeys to compare the frequencies of two mechanical vibrations applied sequentially to the tip of a finger and to report which of the two stimuli had the higher frequency. This task requires remembering the first frequency during the delay period between the two stimuli. Recordings were made from neurons in the inferior convexity of the prefrontal cortex (PFC) while the monkeys performed the task. We report neurons that fire persistently during the delay period, with a firing rate that is a monotonic function of the frequency of the first stimulus. Separately from, and in addition to, their correlation with the first stimulus, the delay period firing rates of these neurons were correlated with the behavior of the monkey, in a manner consistent with their interpretation as the neural substrate of working memory during the task. Most neurons had firing rates that varied systematically with time during the delay period. We suggest that this time-dependent activity may encode time itself and may be an intrinsic part of active memory maintenance mechanisms.     

Language learning under working memory constraints correlates with microstructural differences in the ventral language pathway

The present study combined behavioral measures and diffusion tensor imaging to investigate the neuroanatomical basis of language learning in relation to phonological working memory (WM). Participants were exposed to simplified artificial languages under WM constraints. The results underscore the role of the rehearsal subcomponent of WM in successful speech segmentation and rule learning. Moreover, when rehearsal was blocked task performance was correlated to the white matter microstructure of the left ventral pathway connecting frontal and temporal language-related cortical areas through the extreme/external capsule. This ventral pathway may therefore play an important additional role in language learning when the main dorsal pathway-dependent rehearsal mechanisms are not available.     

The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval

Age-related declines in source memory have been observed for various stimuli and associated details. These impairments may be related to alterations in brain regions contributing to source memory via material-independent processes and/or regions specialized for processing specific materials. Using event-related functional magnetic resonance imaging, we investigate the effects of aging on source memory and associated neural activity for words and objects. Source accuracy was equally impaired in older adults for both materials. Imaging data revealed both groups recruited similar networks of regions to support source memory accuracy irrespective of material, including parietal and prefrontal cortices (PFC) and the hippocampus. Age-related decreases in material-independent activity linked to postretrieval monitoring were observed in right lateral PFC. Additionally, age-related increases in source accuracy effects were shown in perirhinal cortex, which were positively correlated with performance in older adults, potentially reflecting functional compensation. In addition to group differences in material-independent regions, age-related crossover interactions for material-dependent source memory effects were observed in regions selectively engaged by objects. These results suggest that older adults' source memory impairments reflect alterations in regions making material-independent contributions to source memory retrieval, primarily the lateral PFC, but may be further impacted by changes in regions sensitive to particular materials.     

Dissociation of verbal working memory system components using a delayed serial recall task

Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of component processes in verbal working memory. Based on behavioral research using manipulations of verbal stimulus type to dissociate storage, rehearsal, and executive components of verbal working memory, we designed a delayed serial recall task requiring subjects to encode, maintain, and overtly recall sets of verbal items for which phonological similarity, articulatory length, and lexical status were manipulated. By using a task with temporally extended trials, we were able to exploit the temporal resolution afforded by fMRI to partially isolate neural contributions to encoding, maintenance, and retrieval stages of task performance. Several regions commonly associated with maintenance, including supplementary motor, premotor, and inferior frontal areas, were found to be active across all three trial stages. Additionally, we found that left inferior frontal and supplementary motor regions showed patterns of stimulus and temporal sensitivity implicating them in distinct aspects of articulatory rehearsal, while no regions showed a pattern of sensitivity consistent with a role in phonological storage. Regional modulation by task difficulty was further investigated as a measure of executive processing. We interpret our findings as they relate to notions about the cognitive architecture underlying verbal working memory performance.     

Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks

Single cells were recorded with 'tetrodes' in regions of the rat medial prefrontal cortex, including those which are targets of hippocampal afferents, while rats were performing three different behavioral tasks: (i) an eight-arm radial maze, spatial working memory task, (ii) a figure-eight track, delayed spatial alternation task, and (iii) a random food search task in a square chamber. Among 187 recorded units, very few exhibited any evidence of place-specific firing on any of the behavioral tasks, except to the extent that different spatial locations were related to distinct phases of the task. Furthermore, no prefrontal unit showed unambiguous spatially dependent delay activity that might mediate working memory for spatial locations. Rather, the cells exhibited diverse correlates that were generally associated with the behavioral requirements of performing the task. This included firing related to intertrial intervals, onset or end of trials, selection of specific arms on the eight-arm radial maze, delay periods, approach to or departure from goals, and selection of paths on the figure-eight track. Although a small number of cells showed similar behavioral correlates across tasks, the majority of cells showed no consistent correlate when recorded across multiple tasks. Furthermore, some units did not exhibit altered firing patterns in any of the three tasks, while others showed changes in firing that were not consistently related to specific behaviors or task components. These results are in agreement with previous lesion and behavioral studies in rats that suggest a prefrontal cortical role in encoding 'rules' (i.e. structural features) or behavioral sequences within a task but not in encoding allocentric spatial information. Given that the hippocampal projection to this cortical region is capable of undergoing LTP, our data lead to the hypothesis that the role of this projection is not to impose spatial representations upon prefrontal activity, but to provide a mechanism for learning the spatial context in which particular behaviors are appropriate.      

A common neural network for cognitive reserve in verbal and object working memory in young but not old

Epidemiologic evidence suggests that cognitive reserve (CR) mitigates the effects of aging on cognitive function. The goal of this study was to see whether a common neural mechanism for CR could be demonstrated in brain imaging data acquired during the performance of 2 tasks with differing cognitive processing demands. Young and elder subjects were scanned with functional magnetic resonance imaging (fMRI) while performing a delayed item response task that used either letters (40 young, 18 old) or shapes (24 young, 21 old). Difficulty or load was manipulated by varying the number of stimuli that were presented for encoding. Load-dependent fMRI signal corresponding to each trial component (stimulus presentation, retention delay, and probe) and task (letter or shape) was regressed onto 2 putative CR variables. Canonical variates analysis was applied to the resulting maps of regression coefficients, separately for each trial component, to summarize the imaging data--CR relationships. There was a latent brain pattern noted in the stimulus presentation phase that manifested similar relationships between load-related encoding activation and CR variables across the letter and shape tasks in the young but not the elder age group. This spatial pattern could represent a general neural instantiation of CR that is affected by the aging process.     

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.     

The different neural correlates of action and functional knowledge in semantic memory: an FMRI study

Previous reports suggest that the internal organization of semantic memory is in terms of different "types of knowledge," including "sensory" (information about perceptual features), "action" (motor-based knowledge of object utilization), and "functional" (abstract properties, as function and context of use). Consistent with this view, a specific loss of action knowledge, with preserved functional knowledge, has been recently observed in patients with left frontoparietal lesions. The opposite pattern (impaired functional knowledge with preserved action knowledge) was reported in association with anterior inferotemporal lesions. In the present study, the cerebral representation of action and functional knowledge was investigated using event-related analysis of functional magnetic resonance imaging data. Fifteen subjects were presented with pictures showing pairs of manipulable objects and asked whether the objects within each pair were used with the same manipulation pattern ("action knowledge" condition) or in the same context ("functional knowledge" condition). Direct comparisons showed action knowledge, relative to functional knowledge, to activate a left frontoparietal network, comprising the intraparietal sulcus, the inferior parietal lobule, and the dorsal premotor cortex. The reverse comparison yielded activations in the retrosplenial and the lateral anterior inferotemporal cortex. These results confirm and extend previous neuropsychological data and support the hypothesis of the existence of different types of information processing in the internal organization of semantic memory.     

Fragments of a larger whole: retrieval cues constrain observed neural correlates of memory encoding

Laying down a new memory involves activity in a number of brain regions. Here, it is shown that the particular regions associated with successful encoding depend on the way in which memory is probed. Event-related functional magnetic resonance imaging signals were acquired while subjects performed an incidental encoding task on a series of visually presented words denoting objects. A recognition memory test using the Remember/Know procedure to separate responses based on recollection and familiarity followed 1 day later. Critically, half of the studied objects were cued with a corresponding spoken word, and half with a corresponding picture. Regardless of cue, activity in prefrontal and hippocampal regions predicted subsequent recollection of a word. Type of retrieval cue modulated activity in prefrontal, temporal, and parietal cortices. Words subsequently recognized on the basis of a sense of familiarity were at study also associated with differential activity in a number of brain regions, some of which were probe dependent. Thus, observed neural correlates of successful encoding are constrained by type of retrieval cue, and are only fragments of all encoding-related neural activity. Regions exhibiting cue-specific effects may be sites that support memory through the degree of overlap between the processes engaged during encoding and those engaged during retrieval.