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.     

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.     

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.     

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.     

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.     

Dissociable functional cortical topographies for working memory maintenance of voice identity and location

In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance.     

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.     

Specific cerebral networks for maintenance and response organization within working memory as evidenced by the 'double delay/double response' paradigm

Most of the working memory (WM) tasks used in functional imaging studies are based on the principle of the delayed response in which both the storage and the response organization are present during the delay period. It is therefore difficult to isolate activation specific to the storage function from that specific to the organization of the response. To determine the specific neural networks associated with these two WM operations, we performed a functional MRI study in healthy subjects using a new paradigm, 'the double delay/double response' tasks. This paradigm isolates maintenance from response organization by dividing the delay into two separate parts, the first being dedicated to memory, while the second includes response organization. Activation within the dorsolateral prefrontal cortex (DLPFC) followed a relative hemispheric dissociation: activation related to maintenance was predominant in the right DLPFC but was only detected when the load exceeded three items. Activation related to response organization was predominant in the left DLPFC, regardless of whether this response was based on information held in WM ('memory guided') or was independent of WM ('visually-guided'). These results suggest that activation of the DLPFC, should be interpreted in terms of executive processing for both maintenance and response organization.     

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.     

Functional dissociation in right inferior frontal cortex during performance of go/no-go task

The contribution of the right inferior frontal cortex to responseinhibition has been demonstrated by previous studies of neuropsychology,electrophysiology, and neuroimaging. The inferior frontal cortexis also known to be activated during processing of infrequentstimuli such as stimulus-driven attention. Response inhibitionhas most often been investigated using the go/no-go task, andthe no-go trials are usually given infrequently to enhance prepotentresponse tendency. Thus, it has not been clarified whether theinferior frontal activation during the go/no-go task is associatedwith response inhibition or processing of infrequent stimuli.In the present functional magnetic resonance imaging study,we employed not only frequent-go trials but also infrequent-gotrials that were presented as infrequently as the no-go trials.The imaging results demonstrated that the posterior inferiorfrontal gyrus (pIFG) was activated during response inhibitionas revealed by the no-go vs. infrequent-go trials, whereas theinferior frontal junction (IFJ) region was activated primarilyduring processing of infrequent stimuli as revealed by the infrequent-goversus frequent-go trials. These results indicate that the pIFGand IFJ within the inferior frontal cortex are spatially closebut are associated with different cognitive control processesin the go/no-go paradigm.     

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.     

Ventromedial prefrontal cortex is obligatory for consolidation and reconsolidation of object recognition memory

Once consolidated, a long-term memory item could regain susceptibility to consolidation blockers, that is, reconsolidate, upon its reactivation. Both consolidation and reconsolidation require protein synthesis, but it is not yet known how similar these processes are in terms of molecular, cellular, and neural circuit mechanisms. Whereas most previous studies focused on aversive conditioning in the amygdala and the hippocampus, here we examine the role of the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of object recognition memory. Object recognition memory is the ability to discriminate the familiarity of previously encountered objects. We found that microinfusion of the protein synthesis inhibitor anisomycin or the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) into the vmPFC, immediately after training, resulted in impairment of long-term (24 h) but not short-term (3 h) recognition memory. Similarly, microinfusion of anisomycin or APV into the vmPFC immediately after reactivation of the long-term memory impaired recognition memory 24 h, but not 3 h, post-reactivation. These results indicate that both protein synthesis and NMDA receptors are required for consolidation and reconsolidation of recognition memory in the vmPFC.     

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.     

Oscillatory synchrony in the monkey temporal lobe correlates with performance in a visual short-term memory task

Oscillatory synchrony has been proposed to dynamically coordinate distributed neural ensembles, but whether this mechanism is effectively used in neural processing remains controversial. We trained two monkeys to perform a delayed matching-to-sample task using new visual shapes at each trial. Measures of population-activity patterns (cortical field potentials) were obtained from a chronically implanted array of electrodes placed over area V4 and posterior infero-temporal cortex. In correct trials, oscillatory phase synchrony in the beta range (15-20 Hz) was observed between two focal sites in the inferior temporal cortex while holding the sample in short-term memory. Error trials were characterized by an absence of oscillatory synchrony during memory maintenance. Errors did not seem to be due to an impaired stimulus encoding, since various parameters of neural activity in sensory area V4 did not differ in correct and incorrect trials during sample presentation. Our findings suggest that the successful performance of a visual short-term memory task depends on the strength of oscillatory synchrony during the maintenance of the object in short-term memory. The strength of oscillatory synchrony thus seems to be a relevant parameter of the neural population dynamics that matches behavioral performance.     

Age effects on the neural correlates of episodic retrieval: increased cortical recruitment with matched performance

Functional neuroimaging investigations have revealed a range of age-related differences in the neural correlates of episodic memory retrieval. Typically, whereas activity is reduced in older compared with younger adults in some regions, other regions are engaged exclusively, or to a greater extent, in older adults. It is unclear whether such differences merely represent the neural correlates of the lower levels of memory performance and impaired recollection typical of older adults. This issue was addressed in the present event-related functional magnetic resonance imaging study. The level of recollection was matched between groups of healthy younger and older adults for a subset of picture items in a source memory task by manipulating the number of study presentations. Contrasts of the activity elicited by old items attracting correct source judgments and correctly identified new items revealed that the 2 groups recruited many of the same brain regions. However, a striking pattern of age-related differences was also observed. In older adults, retrieval-related increases in activity were more widespread and of greater magnitude than in the young. Moreover, regions demonstrating retrieval-related decreases in activity were almost absent in the older participants. These findings suggest an age-related decline in the efficiency with which neural populations support cognitive function.     

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.     

Neural processes underlying memory attribution on a reality-monitoring task

A relatively common form of memory distortion arises when individuals must discriminate items they have seen from those they have imagined (reality monitoring). The present fMRI investigation (at 1.5 T) focused on the processes that relate to memory assignment regardless of accuracy (e.g. that correspond with the belief that an item was presented as a picture, regardless of whether that belief is correct). Prior to the scan, participants (n = 16) viewed concrete nouns and formed mental images of the object named. Half of the names were followed by the object's photo. During the scan, participants saw the object names and indicated whether the corresponding photo had been studied. Activity in visual-processing regions (including the precuneus and fusiform gyrus) corresponded with the attribution of an item to a pictorial presentation. In contrast, activity in regions thought to be important for self-referential processing (including the ventromedial prefrontal cortex and posterior cingulate gyrus) was associated with attribution to a nonpresented source. These neural findings converge with behavioral evidence indicating that individuals use the amount of different types of information retrieved (e.g. perceptual detail, information about cognitive operations) to determine whether an item was imagined or perceived.     

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.     

Isolating rule- versus evidence-based prefrontal activity during episodic and lexical discrimination: a functional magnetic resonance imaging investigation of detection theory distinctions

Dorsolateral and frontopolar prefrontal cortices (PFCs) are often implicated in neuroimaging studies of memory retrieval, with this activity ascribed to controlled monitoring processes indicative of difficult or demanding retrieval. Difficulty, however, is multiply determined, with success rates governed both by the available evidence and by the nature of decision rules applied to that evidence. Using event-related functional magnetic resonance imaging, we isolated these factors by 1) contrasting different decision rules across matched evidence and 2) manipulating the level of evidence within a fixed decision rule. For identically constructed retrieval probes (1 old and 1 new item), same-different (are these different?) compared with forced-choice (which one is old?) decision rules yielded bilateral dorsolateral and right frontopolar PFC increases. However, these regions were unaffected when the available evidence was greatly lowered within forced-choice decisions. Thus, the regions were simultaneously sensitive to the type of decision rule and yet insensitive to the level of evidence supporting those decisions. Analogous lexical tasks yielded similar patterns, demonstrating that the PFC responses were not episodic memory specific. We discuss the mechanistic differences between same-different versus forced-choice decisions and the implications of these data for current theories of PFC activity during episodic remembering and executive control.     

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.