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Genetic correlations between brain volumes and the WAIS-III dimensions of verbal comprehension, working memory, perceptual organization, and processing speed.

We recently showed that the correlation of gray and white matter volume with full scale IQ and the Working Memory dimension are completely mediated by common genetic factors (Posthuma et al., 2002). Here we examine whether the other WAIS III dimensions (Verbal Comprehension, Perceptual Organization, Processing Speed) are also related to gray and white matter volume, and whether any of the dimensions are related to cerebellar volume. Two overlapping samples provided 135 subjects from 60 extended twin families for whom both MRI scans and WAIS III data were available. All three brain volumes are related to Working Memory capacity (r = 0.27). This phenotypic correlation is completely due to a common underlying genetic factor. Processing Speed was genetically related to white matter volume (r(g) = 0.39). Perceptual Organization was both genetically (r(g) = 0.39) and environmentally (r(e) = -0.71) related to cerebellar volume. Verbal Comprehension was not related to any of the three brain volumes. It is concluded that brain volumes are genetically related to intelligence which suggests that genes that influence brain volume may also be important for intelligence. It is also noted however, that the direction of causation (i.e., do genes influence brain volume which in turn influences intelligence, or alternatively, do genes influence intelligence which in turn influences brain volume), or the presence or absence of pleiotropy has not been resolved yet.

Brain↗

Deficits in spatial working memory after unilateral temporal lobectomy in man.

Forty neurosurgical patients and 20 controls were tested on a series of computerized tasks (the executive golf, structured golf and rotate tasks) designed to investigate spatial working memory. As defined by Olton [Spatial Abilities, Academic Press, New York, 1982], spatial working memory involves the encoding of specific and contextual information within the spatial domain. Right temporal lobectomy patients were significantly impaired on all three tasks, while the left temporal lobectomy patients showed a less significant overall impairment only on the structured golf task. Although there was no statistically significant differences between the two patient groups on the three tasks, the results point towards a robust deficit in spatial memory associated with right temporal lobectomy. The results provide further evidence for the role of the mesial temporal lobe structures in the processing and encoding of spatial information.

Adult↗

Updating information in verbal working memory and executive functioning.

50 older adults (M age=77.9 yr., SD=7.3; 35 women and 15 men) were tested using the updating working-memory task. They were also given the neuropsychological Wisconsin Card Sorting Test, assumed to evaluate executive functioning and the frontal cortex. A factor analysis with age, education, and verbal ability partialled out was computed on the updating task outcomes and resulted in a two-factor solution, indicating that this task requires two independent processes, interpreted as reflecting a storage component and an updating component. Partial correlations with age, education, and verbal ability partialled out indicated that Wisconsin Card Sorting Test measures were significantly associated with the factor supposed to reflect the updating process. Such results appeared consistent with the model of working memory with a central executive system involved in the updating process and related to the executive-frontal functioning, and a phonological loop system involved in the storage of verbal information and not linked to executive-frontal functions.

Aged↗

Functional topography of working memory for face or voice identity.

We used functional magnetic resonance imaging (fMRI) to investigate whether the neural systems for nonspatial visual and auditory working memory exhibits a functional dissociation. The subjects performed a delayed recognition task for previously unfamiliar faces and voices and an audiovisual sensorimotor control task. During the initial sample and subsequent test stimulus presentations, activation was greater for the face than for the voice identity task bilaterally in the occipitotemporal cortex and, conversely, greater for voices than for faces bilaterally in the superior temporal sulcus/gyrus (STS/STG). Ventral prefrontal regions were activated by both memory delays in comparison with the control delays, and there was no significant difference in direct voxelwise comparisons between the tasks. However, further analyses showed that there was a subtle difference in the functional topography for two delay types within the ventral prefrontal cortex. Face delays preferentially activate the dorsal part of the ventral prefrontal cortex (BA 44/45) while voice delays preferentially activate the inferior part (BA 45/47), indicating a ventral/dorsal auditory/visual topography within the ventral prefrontal cortex. The results confirm that there is a modality-specific attentional modulation of activity in visual and auditory sensory areas during stimulus presentation. Moreover, within the nonspatial information-type domain, there is a subtle across-modality dissociation within the ventral prefrontal cortex during working memory maintenance of faces and voices.

Attention↗

Working memory in older subjects: dealing with ongoing and stored information in language comprehension.

The purpose of this experiment was to investigate the role of aging in working memory (WM), or at least the part involved in language comprehension, e.g., a double function of processing the ongoing information and keeping in memory the product of this processing. Young and older subjects were asked to simultaneously detect incongruities in sentences and keep increasing longer series of words (3, 4, or 5) in memory. The difficulty of incongruity detection was manipulated by variation of the number of intervening words (0, 6, or 12) between two critical words. Incongruity detection was assumed to be linked to the processing of information function of working memory. The concurrent mnemonic load consisted of material previously processed, and was assumed to be linked to the storage function of WM. Results showed that an increment in incongruity-detection difficulty led to a greater decrement in accuracy in older than in young subjects, indicating an impairment in the information-processing function. On the other hand, an increment in concurrent mnemonic load led to a slightly smaller decrement in accuracy in older subjects. Furthermore, fewer words from this mnemonic load were recalled in older subjects. It is suggested that older subjects are impaired in coping with both requirements of the task, and tend to sacrifice the storage of information recently processed to devote their resources to the immediate processing component of the task. These results are discussed in relation to their implications for language comprehension.

Adult↗

The role of gestures in spatial working memory and speech.

Co-speech gestures traditionally have been considered communicative, but they may also serve other functions. For example, hand-arm movements seem to facilitate both spatial working memory and speech production. It has been proposed that gestures facilitate speech indirectly by sustaining spatial representations in working memory. Alternatively, gestures may affect speech production directly by activating embodied semantic representations involved in lexical search. Consistent with the first hypothesis, we found participants gestured more when describing visual objects from memory and when describing objects that were difficult to remember and encode verbally. However, they also gestured when describing a visually accessible object, and gesture restriction produced dysfluent speech even when spatial memory was untaxed, suggesting that gestures can directly affect both spatial memory and lexical retrieval.

Adult↗

Working memory and the control of action: evidence from task switching.

A series of 7 experiments used dual-task methodology to investigate the role of working memory in the operation of a simple action-control plan or program involving regular switching between addition and subtraction. Lists requiring switching were slower than blocked lists and showed 2 concurrent task effects. Demanding executive tasks impaired performance on both blocked and switched lists, whereas articulatory suppression impaired principally the switched condition. Implications for models of task switching and working memory and for the Vygotskian concept of verbal control of action are discussed.

Humans↗

More workload on the central executive of working memory, less attention capture by novel visual distractors: evidence from an fMRI study.

The present study examined the interaction of the central executive in working memory with visual attention. Native Chinese participants were given two versions of a number subtraction task, one of low demand and one of high demand, and were asked to ignore a simultaneously presented peripheral distractor. The distractor could be Chinese or Korean characters, familiar or novel to participants, respectively. Compared with the low-demand subtraction task, brain regions commonly associated with central executive functions, including left middle prefrontal cortex, anterior cingulate cortex, and precentral gyrus/sulcus, were significantly activated in the high-demand task. Critically, there was a significant interaction between distractor type and task demand. Novel distractors captured attention and elicited automatic visual analysis, shown by primary visual cortex activation, only when the subtraction task was of low demand but not when it was of high demand. The results provide confirmatory evidence that the extent to which higher level cognitive resources, specifically, the central executive component of working memory, are absorbed by a cognitive task has an impact upon automatic processing that occurs in response to distracting items.

Adult↗

Limitations of the Paced Auditory Serial Addition Test as a measure of working memory in patients with multiple sclerosis.

The Paced Auditory Serial Addition Test (PASAT) is a commonly used procedure that combines elements of both a working memory task and a test of information processing speed. Patients with multiple sclerosis (MS) have consistently been found to be impaired on this test and it has been recommended as a core outcome measure in clinical trials. The standard score for this task is the number of correct responses at each stimulus presentation rate but a concern has been raised that subjects may ignore some test items in order to chunk the information into manageable portions and avoid performing several cognitive tasks simultaneously. To account for this strategy, one can examine the proportion of correct responses that are consecutive (termed dyads), since such responses require that the task be performed according to the instructions. We compared a group of 35 mildly to moderately disabled MS patients and matched healthy controls on the PASAT. The MS patients made significantly fewer correct responses at the 2 slowest presentation rates (2.4, 2.0 s/digit) while their scores at faster rates (1.6, 1.2 s/digit) did not discriminate them from controls as well. Nevertheless, the MS patients' percentage of dyads was significantly lower than that of the control sample across all stimulus presentation rates. While our study supports the use of the PASAT as a test that distinguishes MS patients from healthy individuals, our results also illustrate problems that lie in the interpretation of this difference in performance. It appears that a chunking strategy may be common in the PASAT, particularly as task demands increase, and that this may mask actual performance differences. If so, the total correct response score alone is limited as a measure of working memory and information processing speed. More detailed analyses of PASAT performance, coupled with other measures of information processing, may help clarify the underlying cognitive deficits of MS patients.

Adult↗

Acquisition of shape information in working memory, as a function of viewing time and number of consecutive images: evidence for a succession of discrete storage classes.

The capacity of visual working memory was investigated using abstract images that were slightly distorted NxN (with generally N=8) square lattices of black or white randomly selected elements. After viewing an image, or a sequence of images, the subjects viewed couples of images containing the test image and a distractor image derived from the first one by changing the black or white value of q randomly selected elements. The number q was adjusted in each experiment to the difficulty of the task and the abilities of the subject. The fraction of recognition errors, given q and N was used to evaluate the number M of bits memorized by the subject. For untrained subjects, this number M varied in a biphasic manner as a function of the time t of presentation of the test image: it was on average 13 bits for 1 s, 16 bits for 2 to 5 s, and 20 bits for 8 s. The slow pace of acquisition, from 1 to 8 s, seems due to encoding difficulties, and not to channel capacity limitations. Beyond 8 s, M(t), accurately determined for one subject, followed a square root law, in agreement with 19th century observations on the memorization of lists of digits. When two consecutive 8x8 images were viewed and tested in the same order, the number of memorized bits was downshifted by a nearly constant amount, independent of t, and equal on average to 6-7 bits. Across the subjects, the shift was independent of M. When two consecutive test images were related, the recognition errors decreased for both images, whether the testing was performed in the presentation or the reverse order. Studies involving three subjects, indicate that, when viewing m consecutive images, the average amount of information captured per image varies with m in a stepwise fashion. The first two step boundaries were around m=3 and m=9-12. The data are compatible with a model of organization of working memory in several successive layers containing increasing numbers of units, the more remote a unit, the lower the rate at which it may acquire encoded information.

Functional Laterality↗

Functional MRI of visuospatial working memory in schizotypal personality disorder: a region-of-interest analysis.

BACKGROUND: Functional MRI studies have begun to identify neural networks implicated in visuo-spatial working memory in healthy volunteers and patients with schizophrenia. The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum. METHOD: Unmedicated patients with SPD by DSM-IV criteria and normal controls were assessed with fMRI while performing a visuo-spatial working-memory task. It required the subjects to retain the location of three dots located on the circumference of an imaginary circle and then respond to a query display in which one dot was presented and the subject required to press a button to indicate whether the probe dot location was previously displayed. Subject groups did not differ significantly in spatial memory scores. The exact Talairach and Tournoux coordinates of brain areas previously reported to show activation with spatial memory tasks were assessed. RESULTS: The majority of these locations showed BOLD response activation significantly less in patients during the memory retention period, including the left ventral prefrontal cortex, superior frontal gyrus, intraparietal cortex and posterior inferior gyrus. Regions in the right middle prefrontal and prestriate cortex showed greater activation at a trend level for patients with SPD than for normal controls. In addition, we replicated the findings of increased activation with the task in healthy volunteers in the premotor areas, ventral prefrontal cortex and parietal cortex. CONCLUSIONS: SPD patients show decreased activation compared to healthy volunteers in key frontal regions and we also provided a partial replication of findings reported in healthy subjects.

Adult↗

Dissociation of human caudate nucleus activity in spatial and nonspatial working memory: an event-related fMRI study.

We employed a novel event-related fMRI design and analysis technique to explore caudate nucleus contributions to spatial and nonspatial working memory. The spatial condition of a delayed-response task revealed greater mnemonic activation in four of six subjects when the delay period preceded immediately a probe stimulus requiring an overt motor response, as contrasted with a probe requiring no response. This effect was not seen in frontal or parietal cortical areas, and was seen in the caudate nucleus in a formally identical object condition in just one of six subjects. We hypothesized that this pattern of activity represented spatially dependent motor preparation. A second experiment confirmed this hypothesis: delay-period activity of the caudate nucleus showed greater time dependence in a task that featured spatial and motoric memory demands than in a comparable nonspatial task that featured the same response contingencies. These results suggest an important subcortical locus of the dissociation between spatial and nonspatial working memory, and a role for the human caudate nucleus in the integration of spatially coded mnemonic information with motor preparation to guide behavior.

Adult↗

Modality-specific processing streams in verbal working memory: evidence from spatio-temporal patterns of brain activity.

The present study was concerned with whether there are separate, modality-specific processing "streams" in verbal working memory for information that is heard or read. We used event-related brain potentials (ERPs) recorded from scalp of normal humans to show between-modality differences in spatio-temporal patterns of brain activity during retention in working memory of aurally or visually presented verbal information. The ERP patterns suggested that a sustained, automatically maintained auditory store was activated by auditory presentation and a transient, visual-verbal store was activated by visual presentation. In addition to these modality-specific differences, the ERPs indicated that the phonological loop was activated in both modalities and further suggested that the onset of phonological loop activation was earlier for auditory presentation.

Acoustic Stimulation↗

Neonatal damage of the ventral hippocampus impairs working memory in the rat.

We investigated if a developmental lesion of the ventral hippocampus, studied previously as an animal model of schizophrenia, impairs performance in working memory tests related to the prefrontal cortex. Adult rats with a neonatal or adult excitotoxic lesion of the ventral hippocampus were tested in a continuous delayed alternation and a discrete paired-trial variable-delay alternation task. Performance of rats with the neonatal lesion was impaired as compared with control rats on both tasks, whereas performance of rats with the adult lesion was not altered in either task. The pattern of impaired performance, that worsened with increasing delays in neonatally lesioned rats, resembled that reported previously in animals with adult lesions of the medial prefrontal cortex. These results indicate that an early developmental, but not adult hippocampal, insult impairs performance in tasks sensitive to the integrity of the prefrontal cortex, and suggest that working memory may be compromised by neonatal damage of the ventral hippocampus.

Animals↗

Seeing the content of the mind: enhanced awareness through working memory in patients with visual extinction.

In the present study, we demonstrate that parietal patients with visual extinction show enhanced awareness when there is a match between the current contents of their working memory and the stimuli presented in the visual field. This effect cannot be attributed to automatic bottom-up priming from the presentation of a memory cue, because extinction was reduced only when patients committed the cue to memory, and not when primes were viewed passively or merely identified. The results suggest that reentrant processes, from working memory, modulate awareness.

Aged↗

Neural mechanisms of working memory in ecstasy (MDMA) users who continue or discontinue ecstasy and amphetamine use: evidence from an 18-month longitudinal functional magnetic resonance imaging study.

BACKGROUND: Working memory processing in ecstasy (3,4-methylenedioxymethamphetamine) users is associated with neural alterations as measured by functional magnetic resonance imaging. Here, we examined whether cortical activation patterns change after prolonged periods of continued use or abstinence from ecstasy and amphetamine. METHODS: We used an n-back task and functional magnetic resonance imaging in 17 ecstasy users at baseline (t(1)) and after 18 months (t(2)). Based on the reported drug use at t(2) we separated subjects with continued ecstasy and amphetamine use from subjects reporting abstinence during the follow-up period (n = 9 and n = 8, respectively). RESULTS: At baseline both groups had similar task performance and similar cortical activation patterns. Task performance remained unchanged in both groups. Furthermore, there were no detectable functional magnetic resonance imaging signal changes from t(1) to t(2) in the follow-up abstinent group. However, the continuing users showed a dose-dependent increased parietal activation for the 2-back task after the follow-up period. CONCLUSIONS: Our data suggest that ecstasy use, particularly in high doses, is associated with greater parietal activation during working memory performance. An altered activation pattern might appear before changes in cognitive performance become apparent and, hence, may reflect an early stage of neuronal injury from the neurotoxic drug ecstasy.

Adult↗

Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling.

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.

Adult↗

Attention and working memory in resident anaesthetists after night duty: group and individual effects.

AIMS: To investigate the effects of a single period of night duty on measures of attention and working memory in a group of residents (registrars) in anaesthesiology. Emphasis was placed on individual deficits using a reference point of the equivalent effect of a blood alcohol concentration (BAC) >0.05% determined by other researchers. METHODS: There were 33 subjects aged 26-42 years. Night duty was performed on a weekly basis. Baseline assessments were conducted at either 08 15 or 08 55 preceding night duty and repeated 24-25 hours later, just after the completion of duty. Questionnaires included items regarding duration of sleep and the Stanford Sleepiness Scale. A battery of four reaction time (RT) tasks of increasing difficulty, lasting approximately 35 minutes, was administered on a personal computer. These ranged from simple RT to progressively more complex RT tasks incorporating working memory. A significant change was regarded as >15% deterioration in respect of speed or accuracy. RESULTS: The mean duration of sleep preceding night duty was 7.04 hours and 1.66 hours during the period of night duty. Intergroup comparisons revealed significant prolongation in mean response speed in the first three tests. Mean accuracy was significantly reduced only in respect of the two more complex tests. A >15% deterioration in response speed occurred in up to 30% of subjects on a single task, rising to 52% (17/33) overall. Deterioration occurred in a patchy distribution in most subjects, involving no more than one or two of the four tasks. As regards accuracy, the prevalence of deterioration increased with task complexity. CONCLUSIONS: Results are in general agreement with previous group analyses. A new dimension was added by the analysis of a broad spectrum of individual response to sleep deprivation. The effects of sleep loss in residents cannot be overlooked, even in a relatively benign work schedule.

Adult↗