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An EEG coherence test of the frontal dorsal versus ventral hypothesis in N-back working memory.

We examined Goldman-Rakic's conceptualization of working memory (WM) involving modality-specific reverbatory circuits using electrophysiological measures. An n-back WM task, with either spatial information or object information to be remembered, was administered with EEG coherence used to provide a functional measure of corticocortical communication. Support was not found for modality-specific WM systems in this task. Instead, results suggest that there is a circuit that connects dorsal frontal with dorsal parietal areas which is activated during all levels of the WM vigilance task, regardless of the type of stimuli involved. Data also suggest that left frontal areas are sensitive to the level of difficulty of the WM task (0,1,2, and 3-back), as well as familiarity of task demands. Overall, our results support a model that conceptualizes a unitary WM system rather than a system composed of separate WM circuits for different modalities.

Adult↗

Functional magnetic resonance imaging of working memory among multiple sclerosis patients.

BACKGROUND AND PURPOSE: Verbal working memory (VWM) deficits have been a well-replicated finding among patients with multiple sclerosis (MS). Functional magnetic resonance imaging (FMRI) studies have described a VWM system in healthy samples; however, functional neuroimaging of this system among MS patients is just beginning to appear. METHODS: Fifteen MS patients and 15 sex-, age-, education-, and IQ-matched healthy control (HC) participants completed a 2-Back VWM task as whole-brain FMRI was conducted. RESULTS: Each group exhibited increased brain activity compared to the O-Back control task in regions associated with the 2-Back in previous neuroimaging studies. These included Broca's area, supplementary motor area (SMA), premotor cortices (PMC), and dorsolateral prefrontal cortices (DLPFC). MS patients exhibited greater cortical activity than did HC participants in left primary motor and somatosensory cortices, PMC, DLPFC, anterior cingulate, and bilateral SMA. MS patients exhibited relatively less activation in Broca's area, bilateral cerebellum, and other regions not typically associated with the 2-Back (e.g., right fusiform gyrus, left lingual gyrus, right hippocampus). Performance accuracy and reaction time did not differ between groups. CONCLUSIONS: Normal performance of a challenging VWM task among high-functioning MS patients is associated with a shift toward greater activity in regions related to sensorimotor functions and anterior attentional/executive components of the VWM system. Posterior memory storage systems appeared unaffected, while portions of the visual processing and subvocal rehearsal systems were less active. Although a shift in neural activity was noted relative to HC participants, deviation from regions normally involved in VWM function was not observed in this patient sample.

Adult↗

The spacing effect depends on an encoding deficit, retrieval, and time in working memory: evidence from once-presented words.

The spacing effect in list learning occurs because identical massed items suffer encoding deficits and because spaced items benefit from retrieval and increased time in working memory. Requiring the retrieval of identical items produced a spacing effect for recall and recognition, both for intentional and incidental learning. Not requiring retrieval produced spacing only for intentional learning because intentional learning encourages retrieval. Once-presented words provided baselines for these effects. Next, massed and spaced word pairs were judged for matches on their first three letters, forcing retrieval. The words were not identical, so there was no encoding deficit. Retrieval could and did cause spacing only for the first word of each pair; time in working memory, only for the second.

Humans↗

Behavioral inhibition, self-regulation of motivation, and working memory in children with attention deficit hyperactivity disorder.

We examined 3 aspects of Barkley's (1997) recent model of Attention Deficit Hyperactivity Disorder (ADHD)--behavioral inhibition, self-regulation of motivation, and working memory utilizing 152 elementary school children ages 7 to 12. Seventy-six children with ADHD and 76 children without a psychiatric diagnosis completed the stop-signal task, a computerized Digit Span Task requiring concurrent storage and processing, and the Kaufman Brief Intelligence Test during a 1-hr testing session. Parent and teacher ratings were also obtained on the Conners Parent Rating Scale-Revised: Long Version (Conners, 1997), and the Conners Teacher Rating Scale-Revised: Long Version (Conners, 1997), respectively. Results indicated that children with ADHD had deficits in inhibitory control, working memory, and short-term memory relative to children without the disorder. Contrary to our prediction, the groups did not differ in their responsiveness to external reinforcement. In addition, children with and without ADHD had similar self-perceptions of their performances during the experimental session. Future directions for specifying childhood difficulties in inhibitory control and memory processes are discussed.

Arousal↗

Age-related changes in calcium homeostatic mechanisms in synaptosomes in relation with working memory deficiency.

Aging is associated with alterations in different systems that govern neuronal calcium homeostasis. This study was designed to determine whether any of these alterations may contribute to the decline in spatial working memory that is observed in old rats. Several parameters [initial (5 s) and steady state (15 min) 45Ca2+ uptake, FCCP-releaseable 45Ca2+, [Ca2+]i levels, depolarization-induced phosphoprotein (P97, PP65, P42) dephosphorylation and acetylcholine levels and release) involved in calcium homeostasis/signaling were determined in whole brain synaptosomes derived from adult (9-month-old) and old (24-month-old) rats that were evaluated for spatial memory performance in the eight-arm radial maze. The neurochemical analysis indicated that both the 9- and 24-month-old rats were impaired with respect to 3-month-old animals. When learners (animals reaching criterion; RC) were compared to memory impaired rats (MI), it was found that the FCCP-releaseable 45Ca2+ of synaptosomes, that reflects mitochondrial calcium, was lower in the MI than the RC rats and was correlated with the behavioral performance of the rats in their first testing sessions. The results suggest that the loss of calcium uptake capacity in synaptic mitochondria during aging may be associated with impaired working memory in old animals.

Acetylcholine↗

Intersentential syntactic context effects on comprehension: the role of working memory.

The study investigated the influence of a syntactically biasing context sentence on the processing of syntactically complex object-first relative clauses and even more complex object-first complement clauses in readers with individual differences in working memory. Behavioral as well as brain responses (event-related potentials, ERPs) were recorded from two groups of participants with either a high or a low working memory span. The behavioral data taken from a post-sentence comprehension question task indicate an intersentential syntactic contextual influence on the comprehension of object-first relative clauses for low span readers, but not for high span readers. The on-line ERP measures taken at the disambiguating item revealed for the high span readers a main effect of structure (subject- versus object-first) i.e., a P600, independent of context. Low span readers, in contrast, did not show any P600 structure effect. Thus, the combined data indicate a differential context effect on sentence comprehension in low and high span readers. High span readers parse the incoming information independent of intersentential context, whereas low span readers use the intersentential context off-line.

Adult↗

The bailiwick of visuo-spatial working memory: evidence from unilateral spatial neglect.

An accurate representation of the visual environment is crucial for successful interaction with objects in that environment. The means by which that representation is formed in working memory is a major focus of the issues and research discussed in this paper. The discussion draws on experimental studies of healthy adults and of patients with impairments of visual perceptual processing or of visuo-spatial mental representation. These disorders are most commonly linked with the disorder referred to clinically as unilateral spatial neglect. We discuss the observed dissociation between perceptual neglect and representational neglect, and the phenomenon of implicit processing of information in the neglected hemifield. In so doing we explore the implications of the findings from this literature for the development of theories of visuo-spatial working memory.

Attention↗

The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences.

Using an event-related functional MRI design, we explored the relative roles of dorsal and ventral prefrontal cortex (PFC) regions during specific components (Encoding, Delay, Response) of a working memory task under different memory-load conditions. In a group analysis, effects of increased memory load were observed only in dorsal PFC in the encoding period. Activity was lateralized to the right hemisphere in the high but not the low memory-load condition. Individual analyses revealed variability in activation patterns across subjects. Regression analyses indicated that one source of variability was subjects' memory retrieval rate. It was observed that dorsal PFC plays a differentially greater role in information retrieval for slower subjects, possibly because of inefficient retrieval processes or a reduced quality of mnemonic representations. This study supports the idea that dorsal and ventral PFC play different roles in component processes of working memory.

Adult↗

Synchronization between prefrontal and posterior association cortex during human working memory.

We measured coherence between the electroencephalogram at different scalp sites while human subjects performed delayed response tasks. The tasks required the retention of either verbalizable strings of characters or abstract line drawings. In both types of tasks, a significant enhancement in coherence in the theta range (4-7 Hz) was found between prefrontal and posterior electrodes during 4-s retention intervals. During 6-s perception intervals, far fewer increases in theta coherence were found. Also in other frequency bands, coherence increased; however, the patterns of enhancement made a relevance for working memory processes seem unlikely. Our results suggest that working memory involves synchronization between prefrontal and posterior association cortex by phase-locked, low frequency (4-7 Hz) brain activity.

Cerebral Cortex↗

Spatial working memory activity of the caudate nucleus is sensitive to frame of reference.

We used event-related fMRI to test the hypothesis that the caudate nucleus is preferentially recruited by a spatial working memory task employing egocentrically defined stimuli, which are amenable to transformation into a motor code, as contrasted with allocentrically defined stimuli, which are not. Our results revealed greater delay-epoch activity in egocentric than in allocentric trials in the caudate nucleus and trends in the same direction in the putamen and the lateral premotor cortex (PMC). Response-related activity was greater for egocentric trials in the lateral PMC. We propose that the neostriatum, possibly interacting with the PMC, may contribute to the sensory-motor transformation necessary to establish a prospective motor code (e.g., the representation of a saccade or a grasp). In addition, the PMC may participate in decision-making processes, prompted by the onset of the probe stimulus, that employ this prospective motor information. This model accounts for the empirical evidence that motor distraction disrupts spatial working memory performance.

Adult↗

Patterns of verbal long-term and working memory performance reveal deficits in strategic processing in children with frontal infarcts related to sickle cell disease.

Frontal brain regions are thought to mediate strategic processes that facilitate memory. We hypothesized that children with frontal cerebral infarcts related to sickle cell disease (SCD) would exhibit impairments in long-term and working memory as a result of disruptions in strategic processing. Word-list learning and digit span tasks were used to assess verbal memory and strategic processing in 21 children with SCD without infarcts (controls) and in 10 children with SCD with frontal infarcts. On the word-list learning task, children with frontal infarcts performed more poorly in terms of learning and free recall, although recognition and cued recall were adequate; this pattern suggested intact encoding and storage with impaired retrieval. Children with frontal infarcts performed more poorly on backward digit span, although forward digit span was adequate; this pattern suggested intact maintenance with impaired manipulation of information in working memory. Overall, these findings support the notion that disruptions in strategic processing contribute to memory impairments in children with frontal infarcts.

Adolescent↗

Relationship between morphine and etonitazene-induced working memory impairment and analgesia.

An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment was linearly related to the log of the administered dose, and the log-dose relationships were parallel. The regression lines calculated for each parameter for both drugs were parallel thus allowing us to calculate the potency: etonitazene proved to about 1000 times more potent than morphine in terms of correct arm entries, the number of errors and the total time taken to complete the task. Moreover, the progressive cognitive impairment produced by both opiates was closely related to an increase in analgesic effect. Pretreatment with naloxone (5 mg/kg i.p.) completely antagonised the disruptive effect of the opiates on working memory. The importance of the mu subtype opiate receptor in cognitive processes is discussed.

Analgesia↗

EEG alpha synchronization and functional coupling during top-down processing in a working memory task.

Electroencephalogram (EEG) alpha (around 10 Hz) is the dominant rhythm in the human brain during conditions of mental inactivity. High amplitudes as observed during rest usually diminish during cognitive effort. During retention of information in working memory, however, power increase of alpha oscillations can be observed. This alpha synchronization has been interpreted as cortical idling or active inhibition. The present study provides evidence that during top-down processing in a working memory task, alpha power increases at prefrontal but decreases at occipital electrode sites, thereby reaching a state in which alpha power and frequency become very similar over large distances. Two experimental conditions were compared. In the first, visuospatial information only had to be retained in memory whereas the second condition additionally demanded manipulation of the information. During the second condition, stronger alpha synchronization at prefrontal sites and larger occipital alpha suppression was observed as compared to that for pure retention. This effect was accompanied by assimilation of prefrontal and occipital alpha frequency, stronger functional coupling between prefrontal and occipital brain areas, and alpha latency shifts from prefrontal cortex to primary visual areas, possibly indicating the control of posterior cortical activation by anterior brain areas. An increase of prefrontal EEG alpha amplitudes, which is accompanied by a decrease at posterior sites, thus may not be interpreted in terms of idling or "global" inhibition but may enable a tight functional coupling between prefrontal cortical areas, and thereby allows the control of the execution of processes in primary visual brain regions.

Adult↗

Orthography effect on brain activities in the working memory process for phonologically ambiguous syllables: a functional magnetic resonance imaging study using Japanese speakers.

English /l/ and /r/ sounds are not distinctive for Japanese speakers and they are loosely associated with corresponding graphemes. The purpose of this study was to investigate the brain activities in the memory process for the graphemes containing 'l' and 'r' in Japanese speakers. Two functional magnetic resonance imaging (at 1.5 T) experiments was conducted using syllable working memory tasks. The task using 'l' and 'r' syllables was coupled with either task using 'b' and 'n' syllables (l/r versus b/n block-designed experiment), or 'd' and 'n' syllables (l/r versus d/n block-designed experiment). The results revealed that the l/r working memory tasks induced augmented activation specifically in the right middle frontal gyrus (BA9, 46) and the right superior parietal lobule (BA7), compared with the b/n or d/n tasks. The results indicate that a visually-biased memory process (i.e. excessive visual rehearsal or monitoring) was executed for phonologically ambiguous syllables. Significant activation in the left inferior frontal gyrus was not observed only in the b/n task, probably because articulatory contrast between /b/ and /n/ sounds was highly clear for Japanese speakers.

Adult↗

Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia.

BACKGROUND: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia. However, the specific cognitive processes underlying impaired performance have not been identified. Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit. METHODS: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory-letter-number (LN) span. RESULTS: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r = 0.74). Between-group WCST differences were eliminated when we covaried LN span. Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration. CONCLUSION: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia.

Adult↗

Spatial mapping, working memory, and the fimbria-fornix system.

Rats with lesions severing either the subcallosal fornix (Fo) or the medial half of the fimbria (Fi) were used. They were compared with control (Co) animals in a working memory task (serial alternation) and a reference memory task (cue-guided alternation). Neither task required spatial mapping strategy. Damaging the Fi, but not the Fo, caused a severe deficit in the serial alternation task. Analysis of individual performance revealed that Fi rats either adopted a "side strategy, " resulting in worse than chance performance. This active perseveration required intact working memory mechanism. In the cue-guided alternation task, Fo animals proved superior to Co and Fi rats. These findings are inconsistent with notions that the exclusive role of the hippocampus is spatial mapping or storing of recent memories. They indicate also differential involvement of the fimbria and fornix fibers in behavior.

Animals↗

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Adult↗

Analysis of recurrent cortico-basal ganglia-thalamic loops for working memory.

We analyse a simplified form of the frontal lobe architecture of cortico-basal ganglia-thalamo-cortical loops to determine the manner in which they can learn temporal sequences as part of working memory activity. In particular, we consider how the temporal duration of activity can arise in this setting. We start from a hard-wired version in which temporally extended activity is created by the 'long' loop of cortex --> basal ganglia --> thalamus --> cortex, and show it arises from a near saddle-node bifurcation. The manner in which the transition between patterns occurs is also considered. This is then extended to analyse the temporal sequence storage and regeneration abilities of trained networks with a similar architecture. The temporal dynamics of this activity is also analysed. Implications of this for other working memory activities and for understanding the architecture of the frontal lobes are discussed in conclusion.

Animals↗