Hemispheric asymmetry of spatial working memory deficit in schizophrenia.

Spatial working memory function was assessed in schizophrenia patients, hypothetically 'psychosis-prone' individuals who report unusual perceptual experiences and normal control subjects with an oculomotor delayed response task. Past studies point to the important role of dorsolateral prefrontal system in spatial working memory deficits of schizophrenia patients. In order to better understand the processes precipitating in working memory deficit, two types of working memory errors were examined: never-corrected vs. immediately-corrected errors. In schizophrenia patients, the loss of spatial representation in working memory, as captured by the presence of never-corrected errors, was much more severe when the target was presented in the right visual hemifield than when the target was presented in the left visual field. The same pattern was observed in healthy, psychometrically ascertained 'psychosis-prone' subjects. Therefore, the observed asymmetry of spatial working memory deficit seems unlikely to be a mere side-effect of medication or hospitalization. Normal control subjects did not show hemispheric asymmetry in error patterns. These results suggest that the loss of spatial representation during a delay period may be more severe in the left hemisphere in patients with schizophrenia and in 'psychosis-prone' individuals.     

Dopamine and frontostriatal networks in cognitive aging

Recent studies have linked dopamine to differences in behavior and brain activity in normal individuals. We explored these relationships in older and younger adults by investigating how functional connectivity between the striatum and prefrontal cortex is related to caudate dopamine and verbal working memory task performance. We studied 12 young and 18 older participants with functional magnetic resonance imaging (fMRI) during this task, and used positron emission tomography with the tracer 6-[¹⁸F]-fluoro-L-m-tyrosine (FMT) to assess dopamine synthesis capacity. Younger adults had a greater extent of frontal caudate functional connectivity during the load-dependent delay period of the working memory task than the older participants. Across all subjects, the extent of this functional connectivity was negatively correlated with dopamine synthesis capacity, such that participants with the greatest connectivity had the lowest caudate 6-[¹⁸F]-fluoro-L-m-tyrosine (FMT) signal. Additionally, the extent of functional connectivity was positively correlated with working memory performance. Overall these data suggest interdependencies exist between frontostriatal functional connectivity, dopamine, and working memory performance and that this system is functioning suboptimally in normal aging.     

Physical activity and working memory in healthy older adults: An ERP study

This study examined the effects of physical activity on working memory in older adults using both behavioral and neuroelectric measures. Older adults were assigned to either a higher or lower physical activity group, and event‐related potentials were recorded during assessments of a modified Sternberg task. The results indicated that older adults in the higher physical activity group exhibited shorter response times, independent of the working memory load. Enhanced P3 and N1 amplitudes and a decreased P3 latency were observed in the higher physical activity group. These findings suggested that physical activity facilitates working memory by allocating more attentional resources and increasing the efficiency of evaluating the stimulus during the retrieval phase as well as engaging more attentional resources for the early discriminative processes during the encoding phase of a working memory task.     

Effects of aging and working memory demands on prospective memory

The current study used event-related brain potentials (ERPs) to examine the effects of aging, increasing the working memory demands of the ongoing activity, and a prospective memory load on the neural correlates of prospective remembering and target recognition. The behavioral data revealed that the success of prospective memory was sensitive to working memory load in younger, but not older, adults and that a prospective memory load had a greater effect on the performance of older adults than that of younger adults. The ERP data revealed age-related differences in the neural correlates of the detection of prospective cues, post-retrieval processes that support prospective memory, and target recognition. Our results support the hypothesis that there are age-related differences in the ability to recruit preparatory attentional processes that underlie prospective memory, and demonstrate that younger and older adults may recruit somewhat different neural generators to support prospective memory and working memory.     

Family resemblance: Ten family members with prosopagnosia and within-class object agnosia

We report on neuropsychological testing done with a family in which many members reported severe face recognition impairments. These 10 individuals were high functioning in everyday life and performed normally on tests of low-level vision and high-level cognition. In contrast, they showed clear deficits with tests requiring face memory and judgements of facial similarity. They did not show deficits with all aspects of higher level visual processing as all tested performed normally on a challenging facial emotion recognition task and on a global–local letter identification task. On object memory tasks requiring recognition of particular cars and guns, they showed significant deficits so their recognition impairments were not restricted to facial identity. These results strongly suggest the existence of a genetic condition leading to a selective deficit of visual recognition.     

Family resemblance: ten family members with prosopagnosia and within-class object agnosia

We report on neuropsychological testing done with a family in which many members reported severe face recognition impairments. These 10 individuals were high functioning in everyday life and performed normally on tests of low-level vision and high-level cognition. In contrast, they showed clear deficits with tests requiring face memory and judgements of facial similarity. They did not show deficits with all aspects of higher level visual processing as all tested performed normally on a challenging facial emotion recognition task and on a global-local letter identification task. On object memory tasks requiring recognition of particular cars and guns, they showed significant deficits so their recognition impairments were not restricted to facial identity. These results strongly suggest the existence of a genetic condition leading to a selective deficit of visual recognition.     

Delayed-execute prospective memory performance: the effects of age and working memory

This study follows the novel delayed-execute prospective memory paradigm, which involves briefly delaying the execution of an intended action, a task that has been shown to produce substantial age effects. During the ongoing task, sentences were presented, and participants had to answer reading-comprehension questions and general knowledge questions. In the prospective memory task, the participant was to press a key after the presentation of a specific cue in the sentences—but not before a subsequent phase of the ongoing task was reached. In contrast to previous studies using older participants taken from very broadly defined age ranges, this study examines development of delayed-execute prospective memory more precisely by examining a total of 4 age groups: a younger age group (age range = 22-31; n = 27), a young-old age group (age range = 60-69; n = 34), a middle-old age group (age range = 70-79; n = 31), and an old-old age group (age range = 80-91; n = 35). This study investigates the dependence of (age-related) delayed-execute prospective memory performance on working memory capacity by disrupting the phonological loop during the delay period as well as its dependence on neuropsychological processes such as inhibitory control and processing speed. The results show that (a) delayed-execute prospective memory particularly declines within the group of older participants, (b) delayed-execute prospective memory is diminished when working memory load is high during the delay period, and (c) age-related performance in delayed-execute prospective memory may be mediated by inhibitory control. The findings are discussed in the context of the frontal lobe hypothesis of cognitive aging.     

Delayed–Execute Prospective Memory Performance: The Effects of Age and Working Memory

This study follows the novel delayed-execute prospective memory paradigm, which involves briefly delaying the execution of an intended action, a task that has been shown to produce substantial age effects. During the ongoing task, sentences were presented, and participants had to answer reading-comprehension questions and general knowledge questions. In the prospective memory task, the participant was to press a key after the presentation of a specific cue in the sentences—but not before a subsequent phase of the ongoing task was reached. In contrast to previous studies using older participants taken from very broadly defined age ranges, this study examines development of delayed-execute prospective memory more precisely by examining a total of 4 age groups: a younger age group (age range = 22–31; n = 27), a young-old age group (age range = 60–69; n = 34), a middle-old age group (age range = 70–79; n = 31), and an old-old age group (age range = 80–91; n = 35). This study investigates the dependence of (age-related) delayed-execute prospective memory performance on working memory capacity by disrupting the phonological loop during the delay period as well as its dependence on neuropsychological processes such as inhibitory control and processing speed. The results show that (a) delayed-execute prospective memory particularly declines within the group of older participants, (b) delayed-execute prospective memory is diminished when working memory load is high during the delay period, and (c) age-related performance in delayed-execute prospective memory may be mediated by inhibitory control. The findings are discussed in the context of the frontal lobe hypothesis of cognitive aging.     

Ventrolateral prefrontal cortex activity associated with individual differences in arbitrary delayed paired-association learning performance: A functional magnetic resonance imaging study

To describe the neural substrates of successful episodic long-term memory encoding, we collected functional magnetic-resonance imaging data as participants completed an arbitrary delayed auditory paired-association learning task. During the task, subjects learned predefined but hidden stimulus pairs by trial and error based on visual feedback. Delay period activity represents the retrieval of the relationship between the cue item and its candidate for associates, that is, working memory. Our hypothesis was that the neural substrates of working memory would be related to long-term memory encoding in a performance-dependent manner. Thus, inter-individual variance in performance following a fixed learning set would be associated with differing neural activations during the delay period. The number of learning trials was adjusted such that performance following completion of the learning set varied across subjects. Each trial consisted of the successive presentation of two stimuli (first stimulus and second stimulus [S2]) with a fixed delay interval, allowing extraction of sustained activity during the delay period. Sustained activities during the delay period were found in the bilateral dorsolateral prefrontal cortex, intraparietal sulcus, and left ventrolateral prefrontal cortex, as well as the premotor and pre-supplementary motor areas. The activities did not change in strength across learning, suggesting that these effects represent working memory components. The sustained activity in the ventrolateral prefrontal region was correlated with task performance. Task performance was also positively correlated with the decrement in S2/feedback-related activity during learning in the superior temporal sulcus, a region previously shown to be involved in association learning. These findings are consistent with lesion and neuroimaging studies showing that the ventrolateral prefrontal cortex plays an important role in long-term memory encoding, and raise the possibility that working memory processes interact with long-term memory formation as represented by the covariation of activity in the superior temporal sulcus and the ventrolateral prefrontal cortex.     

Encoding and retrieval processes in velo-cardio-facial syndrome (VCFS)

Velo-cardio-facial syndrome (VCFS) is a neurogenetic disorder associated with very high risk for developing schizophrenia. More than half of affected individuals experience transient psychotic symptoms during childhood and a third may develop schizophrenia. Memory regulation deficits disturbing both the encoding and retrieval stages of memory represent core deficits in the cognitive profile associated with schizophrenia. In this study, the authors investigate memory regulation processes in 33 individuals with VCFS along with 33 age- and sex-matched control participants. By using a directed forgetting paradigm and a continuous recognition paradigm, the authors examined selective encoding and suppression of irrelevant contents during retrieval in VCFS. Group comparison analyses revealed comparable performances on selective encoding and recognition accuracy between the VCFS group and control group. However, individuals with VCFS were more likely to make false recognitions and showed deficits in the suppression of irrelevant contents. Results suggest that trait-like deficits of memory regulation in VCFS can be observed during the retrieval stage, while selective encoding remains efficient. Memory regulation processes during retrieval may constitute a trait deficit in the memory profile of individuals with VCFS and may contribute to the cognitive deficits underlying an increased risk for developing schizophrenia in this population.     

Spatial working memory deficits in schizophrenia patients and their first degree relatives from Palau,Micronesia

Spatial working memory deficits associated with dorsolateral prefrontal dysfunction have been found in Caucasian samples of schizophrenia patients and their first‐degree relatives. This study evaluated spatial working memory function in affected and unaffected members of multiplex schizophrenia families from the Republic of Palau to determine whether the spatial working memory deficits associated with schizophrenia extend to this non‐Caucasian population. Palau is an isolated island nation in Micronesia with an elevated prevalence of schizophrenia and an aggregation of cases in large multigenerational families. Our objective was to evaluate the potential for spatial working memory function to serve as one of multiple endophenotypes in a genetic linkage study of these Palauan schizophrenia families. A spatial delayed response task requiring resistance to distraction and a sensorimotor control task were used to assess spatial working memory in 32 schizophrenia patients, 28 of their healthy first‐degree relatives, and 19 normal control subjects. Schizophrenia patients and their relatives were significantly less accurate than normal control subjects on the spatial delayed response task but not on the sensorimotor control task. On both tasks, patients and relatives were slower to respond than the normal controls. There were no age or gender effects on accuracy, and working memory performance in schizophrenia patients was not significantly correlated with medication dosage. In summary, spatial working memory deficits that have been found in Caucasian schizophrenia patients and relatives were confirmed in this isolated Pacific Island family sample. These results suggest that spatial working memory deficits may be a potentially useful addition to the endophenotypic characterization of family members to be used in a comprehensive genome wide linkage analysis of these Palauan families. © 2002 Wiley‐Liss, Inc.     

Spatial working memory deficits in schizophrenia patients and their first degree relatives from Palau,Micronesia

Spatial working memory deficits associated with dorsolateral prefrontal dysfunction have been found in Caucasian samples of schizophrenia patients and their first-degree relatives. This study evaluated spatial working memory function in affected and unaffected members of multiplex schizophrenia families from the Republic of Palau to determine whether the spatial working memory deficits associated with schizophrenia extend to this non-Caucasian population. Palau is an isolated island nation in Micronesia with an elevated prevalence of schizophrenia and an aggregation of cases in large multigenerational families. Our objective was to evaluate the potential for spatial working memory function to serve as one of multiple endophenotypes in a genetic linkage study of these Palauan schizophrenia families. A spatial delayed response task requiring resistance to distraction and a sensorimotor control task were used to assess spatial working memory in 32 schizophrenia patients, 28 of their healthy first-degree relatives, and 19 normal control subjects. Schizophrenia patients and their relatives were significantly less accurate than normal control subjects on the spatial delayed response task but not on the sensorimotor control task. On both tasks, patients and relatives were slower to respond than the normal controls. There were no age or gender effects on accuracy, and working memory performance in schizophrenia patients was not significantly correlated with medication dosage. In summary, spatial working memory deficits that have been found in Caucasian schizophrenia patients and relatives were confirmed in this isolated Pacific Island family sample. These results suggest that spatial working memory deficits may be a potentially useful addition to the endophenotypic characterization of family members to be used in a comprehensive genome wide linkage analysis of these Palauan families.     

Age-related changes in brain activation during a delayed item recognition task

To test competing models of age-related changes in brain functioning (capacity limitation, neural efficiency, compensatory reorganization, and dedifferentiation), young (n=40; mean age=25.1 years) and elderly (n=18; mean age=74.4 years) subjects performed a delayed item recognition task for visually presented letters with three set sizes (1, 3, or 6 letters) while being scanned with BOLD fMRI. Spatial patterns of brain activity corresponding to either the slope or y-intercept of fMRI signal with respect to set size during memory set encoding, retention delay, or probe stimulus presentation trial phases were compared between elder and young populations. Age effects on fMRI slope during encoding and on fMRI y-intercept during retention delay were consistent with neural inefficiency; age effects on fMRI slope during retention delay were consistent with dedifferentiation. None of the other fMRI signal components showed any detectable age effects. These results suggest that, even within the same task, the nature of brain activation changes with aging can vary based on cognitive process engaged.     

Effects of normal aging on event-related desynchronization/synchronization during a memory task in humans

Event-related desynchronization (ERD) and event-related synchronization (ERS) of the 1-20Hz EEG frequencies were studied using wavelet transforms in young (n = 10, mean age 22) and elderly subjects (n = 10, mean age 65) performing an auditory Sternberg memory task with words as stimuli. In both age groups, encoding of the four-word memory set elicited ERS in the theta and alpha frequency range. Theta ERS, and ERD in the alpha and beta bands were observed during retrieval. During encoding, the elderly showed greater alpha ERS and smaller theta ERS. During retrieval, smaller alpha ERD and theta ERS was found in the elderly subjects. Also, in the elderly, beta ERD was elicited in the late time window during retrieval. The statistically significant differences between the age groups were more marked during retrieval than during encoding. The results indicate that although the two groups performed equally well behaviorally in the task and the elderly subjects were cognitively intact, normal aging affects oscillatory theta, alpha and beta responses particularly during retrieval from working memory. The ERD/ERS patterns of the elderly resemble those of children found in a recent study, which might suggest that those memory-related brain processes that evolve later in childhood are the first to be affected in older age.     

Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach.

BACKGROUND: The aim of this study was to assess visual information processing and cognitive functions in unaffected siblings of patients with schizophrenia, bipolar disorder and control subjects with a negative family history. METHODS: The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20) and the controls subjects (N = 20) were matched for age, education, IQ, and psychosocial functioning, as indexed by the Global Assessment of Functioning scale. Visual information processing was measured using two visual backward masking (VBM) tests (target location and target identification). The evaluation of higher cognitive functions included spatial and verbal working memory, Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and recognition. RESULTS: The relatives of schizophrenia patients were impaired in the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42 ms) and in the target location task. Marked dysfunctions were also found in the spatial working memory task and in the long delay verbal recall test. In contrast, the siblings of patients with bipolar disorder exhibited spared performances with the exception of a deficit in the long delay recall task. CONCLUSIONS: Dysfunctions of sensory-perceptual analysis (VBM) and working memory for spatial information distinguished the siblings of schizophrenia patients from the siblings of individuals with bipolar disorder. Verbal recall deficit was present in both groups, suggesting a common impairment of the fronto-hippocampal system.     

Inhibitory control of attention declines more than working memory during normal aging

Changes in frontostriatal systems are believed to reduce the efficiency of executive cognitive functions during normal aging, especially the inhibitory control of attentional and behavioral responses. To characterize changes during normal aging in sensorimotor, working memory and inhibitory attentional systems, we tested 20 healthy elderly subjects (age 65-80) and 28 young adults (age 18-34) using oculomotor paradigms. Visually guided saccades of elderly subjects showed decreased peak velocity and increased reaction time, but not reduced accuracy, indicating selective age-related declines in sensorimotor systems. In an oculomotor working memory task, memory for spatial location information in elderly subjects was as accurate as in young adults. In contrast, elderly subjects demonstrated a significantly reduced ability to voluntarily inhibit eye movements toward flashed targets on an antisaccade task. These findings indicate changes in frontostriatal systems during normal aging that adversely affect volitional inhibitory processes but spare encoding and retrieval components of spatial working memory.     

ERP measures indicate both attention and working memory encoding decrements in aging

We investigated age-related attention and encoding deficits, and their possible interaction, by analyzing visual event-related potentials from young and older adults during a modified Sternberg word recognition task. Young adults performed more accurately, albeit not significantly so. P1 latency was shorter in young adults and correlated negatively with task accuracy (with age partialed out). These data support proposals that P1 indexes attentional suppression, which is less efficient in older adults. N1 was larger in older adults but did not correlate with accuracy. Young adults had higher P2 amplitudes and P2 latency correlated with accuracy (age partialed), supporting the view that semantic operations during encoding are affected by aging. These data indicate that attention (P1) and encoding (P2) decrements may contribute to memory or related cognitive decrements in aging, and P1 and P2 latency measures from appropriate paradigms may be salient ERP markers of these decrements.     

Aging increases the susceptibility to motor memory interference and reduces off-line gains in motor skill learning

Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off-line gains in motor skill learning after practice in children, young, and older adults. Subjects performed a ballistic task (A) followed by an accuracy-tracking task (B) designed to disrupt the consolidation of A. Retention tests of A were performed immediately and 24 hours after B. Older adults showed greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice.     

Active maintenance in prefrontal area 46 creates distractor-resistant memory

How does the brain maintain information in working memory while challenged by incoming distractions? Using functional magnetic resonance imaging (fMRI), we measured human brain activity during the memory delay of a spatial working memory task with distraction. We found that, in the prefrontal cortex (PFC), the magnitude of activity sustained throughout the memory delay was significantly higher on correct trials than it was on error trials. By contrast, the magnitude of sustained activity in posterior areas did not differ between correct and error trials. The correlation of activity between posterior areas was, however, associated with correct memory performance after distraction. On the basis of these findings, we propose that memory representations gain resistance against distraction during a period of active maintenance within working memory. This may be mediated by interactions between prefrontal and posterior areas.     

Effects of traumatic brain injury on working memory-related brain activation in adolescents

Eight adolescents (ages 13-18 years) who sustained traumatic brain injury (TBI) and eight gender- and age-matched typically developing (TD) adolescents underwent event-related functional MRI (fMRI) while performing a Sternberg letter recognition task. Encoding, maintenance, and retrieval were examined with memory loads of one or four items during imaging. Both groups performed above a 70% accuracy criterion and did not differ in performance. TD adolescents showed greater increase in frontal and parietal activation during high-load relative to low-load maintenance than the TBI group. The TBI patients showed greater increase in activation during high-load relative to low-load encoding and retrieval than the TD group. Results from this preliminary study suggest that the capability to differentially allocate neural resources according to memory load is disrupted by TBI for the maintenance subcomponent of working memory. The overrecruitment of frontal and extrafrontal regions during encoding and retrieval following TBI may represent a compensatory process.