A functional MRI study of the influence of practice on component processes of working memory

Previous neuroimaging studies have shown that neural activity changes with task practice. The types of changes reported have been inconsistent, however, and the neural mechanisms involved remain unclear. In this study, we investigated the influence of practice on different component processes of working memory (WM) using a face WM task. Event-related functional magnetic resonance imaging (fMRI) methodology allowed us to examine signal changes from early to late in the scanning session within different task stages (i.e., encoding, delay, retrieval), as well as to determine the influence of different levels of WM load on neural activity. We found practice-related decreases in fMRI signal and effects of memory load occurring primarily during encoding. This suggests that practice improves encoding efficiency, especially at higher memory loads. The decreases in fMRI signal we observed were not accompanied by improved behavioral performance; in fact, error rate increased for high WM load trials, indicating that practice-related changes in activation may occur during a scanning session without behavioral evidence of learning. Our results suggest that practice influences particular component processes of WM differently, and that the efficiency of these processes may not be captured by performance measures alone.     

Distinct neural correlates of associative working memory and long-term memory encoding in the medial temporal lobe

Increasing evidence suggests a role for the hippocampus not only in long-term memory (LTM) but also in relational working memory (WM) processes, challenging the view of the hippocampus as being solely involved in episodic LTM. However, hippocampal involvement reported in some neuroimaging studies using "classical" WM tasks may at least partly reflect incidental LTM encoding. To disentangle WM processing and LTM formation we administered a delayed-match-to-sample associative WM task in an event-related fMRI study design. Each trial of the WM task consisted of four pairs of faces and houses, which had to be maintained during a delay of 10s. This was followed by a probe phase consisting of three consecutively presented pairs; for each pair participants were to indicate whether it matched one of the pairs of the encoding phase. After scanning, an unexpected recognition-memory (LTM) task was administered. Brain activity during encoding was analyzed based on WM and LTM performance. Hence, encoding-related activity predicting WM success in the absence of successful LTM formation could be isolated. Furthermore, regions critical for successful LTM formation for pairs previously correctly processed in WM were analyzed. Results showed that the left parahippocampal gyrus including the fusiform gyrus predicted subsequent accuracy on WM decisions. The right anterior hippocampus and left inferior frontal gyrus, in contrast, predicted successful LTM for pairs that were previously correctly classified in the WM task. Our results suggest that brain regions associated with higher-level visuo-perceptual processing are involved in successful associative WM encoding, whereas the anterior hippocampus and left inferior frontal gyrus are involved in successful LTM formation during incidental encoding.     

Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI

This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM.     

Neural correlates of relational and item-specific encoding during working and long-term memory in schizophrenia

Successful long-term memory (LTM) depends upon effective control of information in working memory (WM), and there is evidence that both WM and LTM are impaired by schizophrenia. This study tests the hypothesis that LTM deficits in schizophrenia may result from impaired control of relational processing in WM due to dorsolateral prefrontal cortex (DLPFC) dysfunction. fMRI was performed on 19 healthy controls and 20 patients with schizophrenia during WM tasks emphasizing relational (reorder trials) versus item-specific (rehearse trials) processing. WM activity was also examined with respect to LTM recognition on a task administered outside the scanner. Receiver operator characteristic analysis assessed familiarity and recollection components of LTM. Patients showed a disproportionate familiarity deficit for reorder versus rehearse trials against a background of generalized LTM impairments. Relational processing during WM led to DLPFC activation in both groups. However, this activation was less focal in patients than in controls, and patients with more severe negative symptoms showed less of a DLPFC increase. fMRI analysis of subsequent recognition performance revealed a group by condition interaction. High LTM for reorder versus rehearse trials was associated with bilateral DLPFC activation in controls, but not in patients who activated the left middle temporal and inferior occipital gyrus. Results indicate that although patients can activate the DLPFC on a structured relational WM task, this activation is less focal and does not translate to high retrieval success, suggesting a disruption in the interaction between WM and LTM processes in schizophrenia.     

Complex span tasks and hippocampal recruitment during working memory

The working memory (WM) system is vital to performing everyday functions that require attentive, non-automatic processing of information. However, its interaction with long term memory (LTM) is highly debated. Here, we used fMRI to examine whether a popular complex WM span task, thought to force the displacement of to-be-remembered items in the focus of attention to LTM, recruited medial temporal regions typically associated with LTM functioning to a greater extent and in a different manner than traditional neuroimaging WM tasks during WM encoding and maintenance. fMRI scans were acquired while participants performed the operation span (OSPAN) task and an arithmetic task. Results indicated that performance of both tasks resulted in significant activation in regions typically associated with WM function. More importantly, significant bilateral activation was observed in the hippocampus, suggesting it is recruited during WM encoding and maintenance. Right posterior hippocampus activation was greater during OSPAN than arithmetic. Persitimulus graphs indicate a possible specialization of function for bilateral posterior hippocampus and greater involvement of the left for WM performance. Recall time-course activity within this region hints at LTM involvement during complex span.     

Circuitry underlying temporally extended spatial working memory

Extended maintenance delays decrease the accuracy of information stored in spatial working memory. In order to elucidate the network underlying sustained spatial working memory, 16 subjects were scanned using fast event-related fMRI as they performed an oculomotor delayed response task containing trials with "short" (2.5 s) or "long" (10 s) delay periods. Multiple cortical and subcortical regions were common to both delay trial types indicating core task regions. Three patterns of activity were found in a subset of core regions that reflect underlying processes: maintenance-related (e.g., left FEF, right supramarginal gyrus (SMG)), response planning-related (e.g., right FEF, SEF), and motor response-related (e.g., lateral cerebellum (declive)) activation. Several regions were more active during long than short delay trials, including multiple sites in DLPFC (BA 9, 46), indicating a circuitry dynamically recruited to support sustained working memory. Our results suggest that specialized brain processes support extended periods of working memory.     

正常老年人无意义图形记忆任务的fMRI研究

目的探讨正常老年人进行记忆任务的实验可行性及激活脑区.方法对11例正常老年志愿者进行无意义图形记忆任务的fMRI实验,实验以组块方式设计,包括第一次记忆组、重复记忆组和再认组.实验数据以SPM99作后处理显示激活脑区.结果 10例受试者的记忆任务完成较好,记忆和再认的激活区域主要集中双侧前额叶、双侧海马旁回(左侧为主)、右侧海马、双侧顶叶(主要为顶上小叶和楔前叶).记忆编码时海马的激活集中在海马头部,而提取时海马的激活则集中在海马的体部及尾部.结论老年人进行fMRI认知实验具有可行性,记忆的编码和提取时需要内侧颞叶海马系统的参与,但所倚重的脑区有微小的差别.     

Working memory effects on semantic processing: priming differences in pars orbitalis

Both working memory (WM) and controlled (attention-mediated) semantic processing functions have been thought to operate as limited capacity systems, but the possible link between these processes has not been investigated. We found that increased WM load attenuated semantic priming (i.e., reduced the response time advantage for semantically primed relative to unprimed items) and changed fMRI signal intensities in brain regions usually associated with both WM (dorsolateral prefrontal cortex) and controlled semantic retrieval (inferior frontal gyrus [IFG], pars orbitalis). fMRI signal changes in dorsolateral prefrontal cortex were negatively correlated with signal changes in pars orbitalis. The findings suggest that controlled semantic processing and working memory share neural system resources.     

When less is more: TPJ and default network deactivation during encoding predicts working memory performance

Previous work has shown that temporo-parietal junction (TPJ), part of a ventral attention network for stimulus-driven reorienting, deactivates during effortful cognitive engagement, along with the default mode network (DMN). TPJ deactivation has been reported both during working memory (WM) and rapid visual search, ostensibly to prevent reorienting to irrelevant objects. We tested whether the magnitude of this deactivation during WM encoding is predictive of subsequent WM performance. Using slow event-related fMRI and a delayed WM task in which distracter stimuli were presented during the maintenance phase, we found that greater TPJ and DMN deactivation during the encoding phase predicted better WM performance. TPJ and DMN, however, also showed several functional dissociations: (1) TPJ exhibited a different task-evoked pattern than DMN, responding to distracters sharing task-relevant features, but not to other types of distracters; and (2) TPJ showed strong functional connectivity with the DMN at encoding but not during distracter presentation. These results provide further evidence for the functional importance of TPJ suppression and indicate that TPJ and DMN deactivation is especially critical during WM trace formation. In addition, the functional connectivity results suggest that TPJ, while not part of the DMN during the resting state, may flexibly “couple” with this network depending on task demands.     

Neuroimaging a single thought: dorsolateral PFC activity associated with refreshing just-activated information.

Neuroimaging studies of human working memory (WM) show conflicting results regarding whether dorsolateral prefrontal cortex (PFC) contributes to maintaining information in consciousness or is recruited primarily when information must be manipulated. Using functional magnetic resonance imaging (fMRI), we looked at a minimal maintenance process--thinking back to a single, just-seen stimulus (refreshing). We found greater activity in left dorsolateral PFC (BA9) when participants refreshed a word compared to reading a word once or a second time. Furthermore, recognition memory was subsequently more accurate and faster for items that had been refreshed, demonstrating that a single thought that maintains activation can have consequences for long-term memory. Our fMRI results call into question any class of models of the functional organization of PFC and WM that associates simple and/or maintenance processes only with ventrolateral PFC or that associates dorsolateral PFC only with more complex processes such as manipulation.     

Similarities and differences in the neural correlates of episodic memory retrieval and working memory

Functional neuroimaging studies have shown that different cognitive functions activate overlapping brain regions. An activation overlap may occur because a region is involved in operations tapped by different cognitive functions or because the activated area comprises subregions differentially involved in each of the functions. To investigate these issues, we directly compared brain activity during episodic retrieval (ER) and working memory (WM) using event-related functional MRI (fMRI). ER was investigated with a word recognition test, and WM was investigated with a word delayed-response test. Two-phase trials distinguished between retrieval mode and cue-specific aspects of ER, as well as between encoding/maintenance and retrieval aspects of WM. The results revealed a common fronto-parieto-cerebellar network for ER and WM, as well as subregions differentially involved in each function. Specifically, there were two main findings. First, the results differentiated common and specific subregions within the prefrontal cortex: (i) left dorsolateral areas were recruited by both functions, possibly reflecting monitoring operations; (ii) bilateral anterior and ventrolateral areas were more activated during ER than during WM, possibly reflecting retrieval mode and cue-specific ER operations, respectively; and (iii) left posterior/ventral (Broca's area) and bilateral posterior/dorsal areas were more activated during WM than during ER, possibly reflecting phonological and generic WM operations, respectively. Second, hippocampal and parahippocampal regions were activated not only for ER but also for WM. This result suggests that indexing operations mediated by the medial temporal lobes apply to both long-term and short-term memory traces. Overall, our results show that direct cross-function comparisons are critical to understand the role of different brain regions in various cognitive functions.     

Common neural substrates for visual working memory and attention

Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.     

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.     

Isolation of saccade inhibition processes: rapid event-related fMRI of saccades and nogo trials

Previous functional magnetic resonance imaging (fMRI) studies have compared saccade trials and nogo trials, which required subjects to look at peripheral visual stimuli and to inhibit automatic saccades evoked by peripheral stimuli, respectively. These studies surprisingly reported no activation differences in cortical saccade regions between the two tasks, despite their opposite response requirements. Here, we re-examined this issue by comparing saccades and nogo trials using a rapid event-related fMRI design in which saccade trials were presented twice as frequently as nogo trials to make the saccade response more prepotent. We hypothesized that this should increase recruitment of response inhibition processes in the nogo task, thereby increasing fMRI activation on nogo trials. Saccade and nogo trials were presented in whole and half trial versions. Whereas whole trials included a trial type instruction followed by peripheral stimulus presentation and subject response, half trials included only the instruction component, allowing us to measure instruction-related activation separately from response-evoked signals for both saccades and nogo trials. Instruction-related activation was greater for nogo versus saccade trials in right frontal eye field, middle frontal gyrus, intraparietal sulcus, and precuneus, which we attribute to a mixture of preparatory and task switching processes. Response-related activation was greater for nogo trials in supplementary eye field, anterior cingulate cortex, inferior frontal gyrus, and right supramarginal gyrus, and we attribute these results to saccade inhibition and other processes associated with an increased requirement for inhibition of the automatic saccade in nogo trials.     

Neurodevelopmental changes in verbal working memory load-dependency: an fMRI investigation

Development of working memory (WM) aptitude parallels structural changes in the frontal–parietal association cortices important for performance within this cognitive domain. The cerebellum has been proposed to function in support of the postulated phonological loop component of verbal WM, and along with frontal and parietal cortices, has been shown to exhibit linear WM load-dependent activation in adults. It is not known if these kinds of WM load-dependent relationships exist for cerebro-cerebellar networks in developmental populations, and whether there are age-related changes in the nature of load-dependency between childhood, adolescence, and adulthood. The present study used fMRI and a verbal Sternberg WM task with three load levels to investigate developmental changes in WM load-dependent cerebro-cerebellar activation in a sample of 30 children, adolescents, and young adults between the ages of 7 and 28. The neural substrates of linear load-dependency were found to change with age. Among adolescents and adults, frontal, parietal and cerebellar regions showed linear load-dependency, or increasing activation under conditions of increasing WM load. In contrast, children recruited only left ventral prefrontal cortex in response to increasing WM load. These results demonstrate that, while children, adolescents, and young adults activate similar cerebro-cerebellar verbal working memory networks, the extent to which they rely on parietal and cerebellar regions in response to increasing task difficulty changes significantly between childhood and adolescence.     

Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex

Recent studies have demonstrated that retinotopic cortex maintains information about visual stimuli during retention intervals. However, the process by which transient stimulus-evoked sensory responses are transformed into enduring memory representations is unknown. Here, using fMRI and short-term visual memory tasks optimized for univariate and multivariate analysis approaches, we report differential involvement of human retinotopic areas during memory encoding of the low-level visual feature orientation. All visual areas show weaker responses when memory encoding processes are interrupted, possibly due to effects in orientation-sensitive primary visual cortex (V1) propagating across extrastriate areas. Furthermore, intermediate areas in both dorsal (V3a/b) and ventral (LO1/2) streams are significantly more active during memory encoding compared with non-memory (active and passive) processing of the same stimulus material. These effects in intermediate visual cortex are also observed during memory encoding of a different stimulus feature (spatial frequency), suggesting that these areas are involved in encoding processes on a higher level of representation. Using pattern-classification techniques to probe the representational content in visual cortex during delay periods, we further demonstrate that simply initiating memory encoding is not sufficient to produce long-lasting memory traces. Rather, active maintenance appears to underlie the observed memory-specific patterns of information in retinotopic cortex.     

Quantitative basal CBF and CBF fMRI of rhesus monkeys using three-coil continuous arterial spin labeling

A three-coil continuous arterial-spin-labeling technique with a separate neck labeling coil was implemented on a Siemens 3T Trio for quantitative cerebral blood flow (CBF) and CBF fMRI measurements in non-human primates (rhesus monkeys). The optimal labeling power was 2 W, labeling efficiency was 92+/-2%, and optimal post-labeling delay was 0.8 s. Gray matter (GM) and white matter (WM) were segmented based on T1 maps. Quantitative CBF were obtained in 3 min with 1.5-mm isotropic resolution. Whole-brain average DeltaS/S was 1.0-1.5%. GM CBF was 104+/-3 ml/100 g/min (n = 6, SD) and WM CBF was 45+/-6 ml/100 g/min in isoflurane-anesthetized rhesus monkeys, with the CBF GM/WM ratio of 2.3+/-0.2. Combined CBF and BOLD (blood-oxygenation-level-dependent) fMRI associated with hypercapnia and hyperoxia were made with 8-s temporal resolution. CBF fMRI responses to 5% CO2 were 59+/-10% (GM) and 37+/-4% (WM); BOLD fMRI responses were 2.0+/-0.4% (GM) and 1.2+/-0.4% (WM). CBF fMRI responses to 100% O2 were -9.4+/-2% (GM) and -3.9+/-2.6% (WM); BOLD responses were 2.4+/-0.7% (GM) and 0.8+/-0.2% (WM). The use of a separate neck coil for spin labeling significantly increased CBF signal-to-noise ratio and the use of small receive-only surface coil significantly increased signal-to-noise ratio and spatial resolution. This study sets the stage for quantitative perfusion imaging and CBF fMRI for neurological diseases in anesthetized and awake monkeys.     

Functional MRI of auditory verbal working memory: long-term reproducibility analysis

Although functional MRI (fMRI) has shown to be a tool with great potential to study the normal and diseased human brain, the large variability in the detected hemodynamic responses across sessions and across subjects hinders a wider application. To investigate the long-term reproducibility of fMRI activation of verbal working memory (WM), eight normal subjects performed an auditory version of the 2-back verbal WM task while fMRI images were acquired. The experiment was repeated nine times with the same settings for image acquisition and fMRI task. Data were analyzed using SPM99 program. Single-session activation maps and multi-subject session-specific activation maps were generated. Regions of interest (ROIs) associated to specific components of verbal WM were defined based on the voxels' coordinates in Talairach space. Visual observation of the multi-subject activation maps showed similar activation patterns, and quantitative analysis showed small coefficients of variance of activation within ROIs over time, suggesting small longitudinal variability of activation. Visual observation of the activation maps of individual sessions demonstrated striking variation of activation across sessions and across subjects, and quantitative analysis demonstrated larger contribution from between-subject variation to overall variation than that from within-subject variation. We concluded that by multi-subject analysis of data from a relatively small number of subjects, reasonably reproducible activation for the 2-back verbal WM paradigm can be achieved. The level of reproducibility encourages the application of this fMRI paradigm to the evaluation of cognitive changes in future investigations. The quantitative estimation of the proportions of within-subject and between-subject variabilities in the overall variability may be helpful for the design of future studies.     

Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance

PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.     

Neuroimaging studies of shifting attention: a meta-analysis

This paper reports a meta-analysis of neuroimaging studies of attention shifting and executive processes in working memory. We analyzed peak activation coordinates from 31 fMRI and PET studies of five types of shifting using kernel-based methods [NeuroImage 19 (2003) 513]. Analyses collapsing across different types of shifting gave more consistent results overall than analysis within individual types, suggesting a commonality across types of shifting. These areas shared substantial, significant overlap with regions derived from kernel-based analyses of reported peaks for executive processes in working memory (WM). The results suggest that there is a common set of brain regions active in diverse executive control operations, including medial prefrontal, superior and inferior parietal, medial parietal, and premotor cortices. However, within several of these regions, different types of switching produced spatially discriminable activation foci. Precise locations of meta analysis-derived regions from both attention shifting and working memory are defined electronically and may be used as regions of interest in future studies.