Related Articles

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in human memory, the necessity of the orbitofrontal cortex for key competencies of working memory remains largely unexplored. We therefore studied human brain lesion patients to determine whether the orbitofrontal cortex is necessary for working memory function, administering subtests of the Wechsler memory scale, the Wechsler adult intelligence scale, and the n-back task to 3 participant groups: orbitofrontal lesions (n = 24), prefrontal lesions not involving orbitofrontal cortex (n = 40), and no brain lesions (n = 54). Orbitofrontal damage was reliably associated with deficits on neuropsychological tests involving the coordination of working memory maintenance, manipulation, and monitoring processes (n-back task) but not on pure tests of working memory maintenance (digit/spatial span forward) or manipulation (digit/spatial span backward and letter–number sequencing). Our findings elucidate a central component of the neural architecture of working memory, providing key neuropsychological evidence for the necessity of the orbitofrontal cortex in executive control functions underlying the joint maintenance, manipulation, and monitoring of information in working memory.

Background

Memory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions.

Methods

Fifteen patients with severe and diffuse TBI and sixteen healthy controls matched by age and years of education were scanned. The neuropsychological assessment included: Letter-number sequencing test (LNS), 2-back task, digit span (forwards and backwards) and the Rivermead profilet. DTI was analyzed by a tract-based spatial statics (TBSS) approach.

Results

Whole brain DTI analysis showed a global decrease in FA values that correlated with the 2-back d-prime index, but not with the Rivermead profile. ROI analysis revealed positive correlations between working memory performance assessed by 2-back d-prime and superior longitudinal fasciculi, corpus callosum, arcuate fasciculi and fornix. Declarative memory assessed by the Rivermead profile scores correlated with the fornix and the corpus callosum.

Conclusions

Diffuse TBI is associated with a general decrease of white matter integrity. Nevertheless deficits in specific memory domains are related to different patterns of white matter damage.

The difference between the speed of simple cognitive processes and the speed of complex cognitive processes has various psychological correlates. However, the neural correlates of this difference have not yet been investigated. In this study, we focused on working memory (WM) for typical complex cognitive processes. Functional magnetic resonance imaging data were acquired during the performance of an N-back task, which is a measure of WM for typical complex cognitive processes. In our N-back task, task speed and memory load were varied to identify the neural correlates responsible for the difference between the speed of simple cognitive processes (estimated from the 0-back task) and the speed of WM. Our findings showed that this difference was characterized by the increased activation in the right dorsolateral prefrontal cortex (DLPFC) and the increased functional interaction between the right DLPFC and right superior parietal lobe. Furthermore, the local gray matter volume of the right DLPFC was correlated with participants' accuracy during fast WM tasks, which in turn correlated with a psychometric measure of participants' intelligence. Our findings indicate that the right DLPFC and its related network are responsible for the execution of the fast cognitive processes involved in WM. Identified neural bases may underlie the psychometric differences between the speed with which subjects perform simple cognitive tasks and the speed with which subjects perform more complex cognitive tasks, and explain the previous traditional psychological findings.

The present study aimed to elucidate the neuro-cognitive processes underlying age-related differences in working memory. Young and middle-aged participants performed a two-choice task with low and a 2-back task with high working memory load. The P300, an event-related potential reflecting controlled stimulus–response processing in working memory, and the underlying neuronal sources of expected age-related differences were analyzed using sLORETA. Response speed was generally slower for the middle-aged than the young group. Under low working memory load the middle-aged participants traded speed for accuracy. The middle-aged were less efficient in the 2-back task as they responded slower while the error rates did not differ for groups. An age-related decline of the P300 amplitude and characteristic topographical differences were especially evident in the 2-back task. A more detailed analysis of the P300 in non-target trials revealed that amplitudes in the young but not middle-aged group differentiate between correctly detected vs. missed targets in the following trial. For these trials, source analysis revealed higher activation for the young vs. middle-aged group in brain areas which support working memory processes. The relationship between P300 and overt performance was validated by significant correlations. To sum up, under high working memory load the young group showed an increased neuronal activity before a successful detected target, while the middle-aged group showed the same neuronal pattern regardless of whether a subsequent target will be detected or missed. This stable memory trace before detected targets was reflected by a specific activation enhancement in brain areas which orchestrate maintenance, update, storage, and retrieval of information in working memory.

Objective

Working memory (WM) deficits have been reported previously in systemic lupus erythematosus (SLE), but the relationship between information processing speed (PS) and WM deficits in SLE is unknown. This study examined whether or not PS slowing could account for the WM deficits observed in SLE.

Method

A visual n-back task was used to measure simple and complex PS and WM in 40 SLE patients and 36 healthy controls. Simple PS was defined as reaction time (RT) to correct responses under a very low WM load condition (0-back), while complex PS was defined as RT to correct responses under moderate and high WM load conditions (1 and 2-back).

Results

The results showed that SLE patients performed as well as the controls at the lower WM load conditions but had fewer correct responses than controls under the highest WM load condition (2-back). SLE patients had slower RTs than controls under all conditions, but they had relatively greater RT slowing than controls under the higher WM load conditions. Further, when RT for simple PS was subtracted from complex PS, SLE patients still showed slower complex PS for the 1 and 2-back compared to controls. Both simple and complex PS slowing were related to poorer accuracy scores on the 2-back condition, only for the SLE group.

Conclusions

The n-back task provides a sensitive measure of PS and WM. The results suggest that PS deficits alone could not account for the WM deficits in SLE. Disease duration, disease activity, and depression did not appear to account for the observed PS and WM deficits.

We investigated the role of dopamine in working memory by examining effects of withdrawing dopaminergic medication in patients with Parkinson’s disease. Resistance to distraction during a delayed response task was abnormally enhanced in Parkinson’s disease patients OFF medication relative to controls. Conversely, performance on a backward digit span test was impaired in these same Parkinson’s disease patients OFF medication. Dopaminergic medication reinstated susceptibility to distraction and backward digit span performance, so that performance of Parkinson’s disease patients ON medication did not differ from that of controls. We hypothesize that the enhanced distractor resistance and impaired backward digit span in Parkinson’s disease reflects low dopamine levels in the striatum, and perhaps upregulated frontal dopamine levels. Dopaminergic medication may reinstate distractibility by normalizing the balance between striatal and prefrontal dopamine transmission.

Rationale

Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.

Objectives

We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group.

Method

We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task.

Results

Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area.

Conclusions

Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics.

Electronic supplementary material

The online version of this article (doi:10.1007/s00213-011-2214-7) contains supplementary material, which is available to authorized users.

Measures of retrieval speed indicated that only a small subset of representations in working memory falls within the focus of attention. An n-back task, which required tracking an item 1, 2, or 3 back in a sequentially presented list, was used to examine the representation and retrieval of recent events and how control processes can be used to maintain an item in focal attention while concurrently processing new information. A speed–accuracy trade-off procedure was used to derive measures of the availability and the speed with which recent events can be accessed. Results converge with other time course studies in demonstrating that attention can be concurrently allocated only to a small number of memory representations, perhaps just 1 item. Measures of retrieval speed further demonstrate that order information is retrieved by a slow search process when an item is not maintained within focal attention.

Introduction: Cognitive deficits are a side-effect of chemotherapy, however pre-treatment research is limited. This study examines neurofunctional differences during working memory between breast cancer (BC) patients and controls, prior to chemotherapy. Methods: Early stage BC females (23), scanned after surgery but before chemotherapy, were individually matched to non-cancer controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing a Visuospatial N-back task and data was analyzed by multiple group comparisons. fMRI task performance, neuropsychological tests, hospital records, and salivary biomarkers were also collected. Results: There were no significant group differences on neuropsychological tests, estrogen, or cortisol. Patients made significantly fewer commission errors but had less overall correct responses and were slower than controls during the task. Significant group differences were observed for the fMRI data, yet results depended on the type of analysis. BC patients presented with increased activations during working memory compared to controls in areas such as the inferior frontal gyrus, insula, thalamus, and midbrain. Individual group regressions revealed a reverse relationship between brain activity and commission errors. Conclusion: This is the first fMRI investigation to reveal neurophysiological differences during visuospatial working memory between BC patients pre-chemotherapy and controls. These results also increase the knowledge about the effects of BC and related factors on the working memory network. Significance: This highlights the need to better understand the pre-chemotherapy BC patient and the effects of associated confounding variables.

Background

Patients with schizophrenia commonly show deficits in working memory on objective neuropsychological measures, and brain imaging studies have documented neural abnormalities during performance of working memory tasks. It remains unclear to what extent such patients are able to accurately gauge the integrity of their working memory in their daily lives. Aims: We evaluated the relationship between subjective rating of working memory integrity in daily life and volumes of the frontal, temporal, and parietal lobes in patients with schizophrenia.

Methods

Participants included 29 patients with schizophrenia and 26 healthy comparison subjects. Participants completed a structural magnetic resonance imaging (MRI) scan, the Self Report form of the Behavioral Rating Scale of Executive Function – Adult version (BRIEF-A), and Digit Span Backwards as an objective measure of working memory. Lobar volumes were obtained using an automated processing package and adjusted for total intracranial volume.

Results

The patient group reported worse working memory in daily life, and performed worse on Digit Span Backwards, than the comparison group. Within the patient group, poorer working memory in daily life was associated with smaller left and right frontal lobe volumes. Shorter backwards digit span was associated with smaller left frontal and left and right temporal lobe volumes.

Conclusions

The significant relationship between frontal lobe volumes and subjective working memory in daily life provides some support for the validity of self report measures of cognitive functioning in patients with schizophrenia, and provides further evidence for a contribution of frontal lobe abnormality to executive dysfunction in the illness.

The goals of the current study were to use behavioral and pupillary measures to examine working memory on a spatial n-back task in 8-20-year-olds with youth-onset psychosis or ADHD (Combined subtype) and healthy controls to determine the contribution of different attentional factors to spatial working memory impairments, and to examine if age-related changes in performance differed across groups. Although both clinical groups had lower perceptual sensitivity on both 0- and 1-back, there was no evidence of an impairment in spatial working memory or differential order effects on the 0-back. Instead, results suggest that both clinical groups had difficulty encoding the stimuli. They also appeared to have difficulty maintaining attention and/or readiness to respond, and, to a lesser extent, recruiting resources on a trial-to-trial basis. It is likely that these attentional problems prevented the clinical groups from encoding the stimuli effectively and contributed to their general performance deficits.

Neuroimaging studies have identified a common network of brain regions involving the prefrontal and parietal cortices across a variety of working memory (WM) tasks. However, previous studies have also reported category-specific dissociations of activation within this network. In this study, we investigated the development of category-specific activation in a WM task with digits, letters, and faces. Eight-year-old children and adults performed a 2-back WM task while their brain activity was measured using functional magnetic resonance imaging (fMRI). Overall, children were significantly slower and less accurate than adults on all three WM conditions (digits, letters, and faces); however, within each age group, behavioral performance across the three conditions was very similar. FMRI results revealed category-specific activation in adults but not children in the intraparietal sulcus for the digit condition. Likewise, during the letter condition, category-specific activation was observed in adults but not children in the left occipital–temporal cortex. In contrast, children and adults showed highly similar brain-activity patterns in the lateral fusiform gyri when solving the 2-back WM task with face stimuli. Our results suggest that 8-year-old children do not yet engage the typical brain regions that have been associated with abstract or semantic processing of numerical symbols and letters when these processes are task-irrelevant and the primary task is demanding. Nevertheless, brain activity in letter-responsive areas predicted children’s spelling performance underscoring the relationship between abstract processing of letters and linguistic abilities. Lastly, behavioral performance on the WM task was predictive of math and language abilities highlighting the connection between WM and other cognitive abilities in development.

Background

In the working population, back disorders are an important reason for sick leave and permanent work inability. In the context of fitting the job to the worker, one of the primary tasks of the occupational health physician is to evaluate the balance between work-related and individual variables. Since this evaluation of work capacity often consists of a physical examination of the back, the objective of this study was to investigate whether a physical examination of the low back, which is routinely performed in occupational medicine, predicts the development of low back pain (LBP).

Methods

This study is part of the Belgian Low Back Cohort (BelCoBack) Study, a prospective study to identify risk factors for the development of low back disorders in occupational settings. The study population for this paper were 692 young healthcare or distribution workers (mean age of 26 years) with no or limited back antecedents in the year before inclusion. At baseline, these workers underwent a standardised physical examination of the low back. One year later, they completed a questionnaire on the occurrence of LBP and some of its characteristics. To study the respective role of predictors at baseline on the occurrence of LBP, we opted for Cox regression with a constant risk period. Analyses were performed separately for workers without any back antecedents in the year before inclusion ('asymptomatic' workers) and for workers with limited back antecedents in the year before inclusion ('mildly symptomatic' workers).

Results

In the group of 'asymptomatic' workers, obese workers showed a more than twofold-increased risk on the development of LBP as compared to non-obese colleagues (RR 2.57, 95%CI: 1.09 – 6.09). In the group of 'mildly symptomatic' workers, the self-reports of pain before the examination turned out to be most predictive (RR 3.89, 95%CI: 1.20 – 12.64).

Conclusion

This study showed that, in a population of young workers wh no or limited antecedents of LBP at baseline, physical examinations, as routinely assessed in occupational medicine, are not useful to predict workers at risk for the development of back disorders one year later.

Background

Working memory (WM) limitations have been suggested as a significant source of the linguistic processing deficits observed in individuals with aphasia (IWA). Digits forward (DF) and digits backward (DB) span tasks are frequently used to study WM in both healthy and clinical populations. Unfortunately, only a handful of studies have explored digit span in IWA.

Aims

The purpose of the current study is to measure the DF and DB spans of IWA and compare their digit spans to a group with right brain damage, but no aphasia (RBD). Additionally, DF and DB span is compared within each group to determine if there is indeed a performance differential that may support the idea that DB is a more difficult WM task in these populations.

Methods and Procedures

Seventeen IWA and 14 individuals with RBD participated in a DF and DB span task. Modifications to the span tasks were implemented to accommodate language deficits. A series of two digits were orally presented to each participant continuing to a maximum of eight digits. There were seven trials per digit series. Participants were asked to point to the correct order of digits on a written 1–9 digit list provided on individual note cards or verbally repeat the numbers if the participant was able to do so.

Outcomes and Results

IWA demonstrated shorter digit spans than the RBD group. Both groups performed worse on the DB span tasks than the DF span tasks.

Conclusions

The results are consistent with previous studies suggesting that DB span is shorter than DF span in other populations and that there are differences in performance on digit span tasks between the two groups. The differences between RBD group and IWA may be explained by decreased attentional capacity or inefficient resource allocation in IWA, or alternatively, a deficient phonological loop. Future studies should explore these possibilities.

A growing number of studies have reported altered functional connectivity in schizophrenia during putatively “task-free” states and during the performance of cognitive tasks. However, there have been few systematic examinations of functional connectivity in schizophrenia across rest and different task states to assess the degree to which altered functional connectivity reflects a stable characteristic or whether connectivity changes vary as a function of task demands. We assessed functional connectivity during rest and during three working memory loads of an N-back task (0-back, 1-back, 2-back) among: (1) individuals with schizophrenia (N = 19); (2) the siblings of individuals with schizophrenia (N = 28); (3) healthy controls (N = 10); and (4) the siblings of healthy controls (N = 17). We examined connectivity within and between four brain networks: (1) frontal–parietal (FP); (2) cingulo-opercular (CO); (3) cerebellar (CER); and (4) default mode (DMN). In terms of within-network connectivity, we found that connectivity within the DMN and FP increased significantly between resting state and 0-back, while connectivity within the CO and CER decreased significantly between resting state and 0-back. Additionally, we found that connectivity within both the DMN and FP was further modulated by memory load. In terms of between network connectivity, we found that the DMN became significantly more “anti-correlated” with the FP, CO, and CER networks during 0-back as compared to rest, and that connectivity between the FP and both CO and CER networks increased with memory load. Individuals with schizophrenia and their siblings showed consistent reductions in connectivity between both the FP and CO networks with the CER network, a finding that was similar in magnitude across rest and all levels of working memory load. These findings are consistent with the hypothesis that altered functional connectivity in schizophrenia reflects a stable characteristic that is present across cognitive states.

Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.

Background

Methamphetamine (METH) is a widely abused psychostimulant that is associated with neurotoxicity and neurocognitive impairments in adults. However, the effects of METH use on neurocognitive performance of adolescents are unclear.

Methods

Fifty-four adolescent METH users and 74 age-matched comparison subjects (ages 12 to 23 years) were evaluated with a battery of neuropsychological tests. The cognitive domains evaluated include psychomotor (Symbol Digit, Trail Making), executive function (Stroop Interference task, Wisconsin Card Sort task), fine-motor speed (Grooved Pegboard), memory (Digit span and Auditory Verbal Learning Task), as well as attention and working memory (California Computerized Assessment package).

Results

METH users were slower on the Stroop Interference task than the comparison subjects (F(1,114)=4.33, p=0.03). METH subjects also performed worse than controls on the Wechsler Adult Intelligence Scale III/Wechsler Intelligence Scale for Children IV (WAIS/WISC) Matrices task (F(1,114)=4.37, p=0.04) and performed significantly worse on the Peg Board task than the comparison subjects for both the dominant (F(1,114)=7.56, p=0.01) and non-dominant (F(1,114)=6.75, p=0.01). Lastly, length of abstinence was associated with improved performance on the Peg Board test with the dominant had (r=−0.34), as well as the WAIS/WISC Forward Digit Span task (r=0.38)

Conclusions

METH use is associated with impaired executive functions in adolescent users.

Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the dopamine transporter genotype (DAT1) is associated with Attention Deficit Hyperactivity Disorder, a childhood disorder marked by poor executive function. We examined whether functional anatomy underlying working memory, a component process of executive function, differed by DAT1 in 7-12 year-old typically developing children. 10/10 and 9/10 carriers performed a verbal n-back task in two functional magnetic resonance imaging (fMRI) runs varying in working memory load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy was superior in 9/10 than 10/10 carriers in the high but not low load runs. Examination of each run separately revealed that frontal-striatal-parietal regions were more activated in 9/10 than 10/10 carriers in the high load run; the groups did not differ in the low load run. Examination of load effects revealed a DAT1 X Load interaction in the right hemisphere in the caudate, our a priori region of interest. Exploratory analysis at a more liberal threshold revealed this interaction in other basal ganglia regions (putamen, and substantial nigra/subthalamic nuclei – SN/STN) and in medial parietal cortex (left precuneus). The striatal and parietal regions were more activated in 9/10 carriers under high than low load, and DAT1 differences (9/10 > 10/10) were evident only under high load. In contrast, SN/STN tended to be more activated in 10/10 carriers under low than high load and DAT1 differences (10/10 > 9/10) were evident only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with reduced performance and a lack of increased basal ganglia involvement under higher working memory demands.

We examined adult age differences in short-term and working memory performance in middle-aged (45–64 years), young-old (65–74 years), old-old (75–89 years) and oldest-old adults (90 years and over) in the Louisiana Healthy Aging Study. Previous research suggests that measures of working memory are more sensitive to age effects than simple tests of short-term memory (Bopp & Verhaeghen, 2005; Myerson, Emery, White, & Hale, 2003). To test this hypothesis, we examined output serial position curves of recall data from three span tasks: forward and backward digit span and size judgment span. Participants’ recall patterns in the size judgment span task revealed that the two oldest groups of adults showed the largest decreases in recall performance across output serial positions, but did not differ significantly from each other. Correlation analyses indicated the strongest negative correlation with age occurred with the size judgment span task. Implications of these findings for understanding strategic processing abilities in late life are discussed.

Background

Patients with depression show abnormalities in the neural circuitry supporting working memory. These abnormalities apparently persist into clinical remission, raising the possibility that they might be trait markers indicating vulnerability to depression.

Methods

We studied 17 young people who had a depressed parent but no personal history of depressive illness (FH) and 15 healthy control subjects with no family history of depression. Participants performed a verbal working memory task of varying cognitive load (n-back) while undergoing functional magnetic resonance imaging scanning. We used multiple regression analyses to assess overall capacity (1-, 2-, 3-back vs. 0-back) as well as linear and quadratic modulation of cognitive demand.

Results

Performance accuracy and response latency did not differ between groups, and overall capacity was similar. However, for both linear and quadratic load response activity, FH participants showed greater activation in lateral occipital cortex, superior temporal cortex, and superior parietal cortex.

Conclusions

Our data suggest that, as in depressed patients, maintenance of task performance in FH participants is associated with a significant increase in the load-response activity of the cortical regions involved in working memory. This neural abnormality could form part of the predisposition to develop depressive disorders.

Difficulties in the ability to update stimuli in working memory (WM) may underlie the problems with regulating emotions that lead to the development and perpetuation of mood disorders such as depression. To examine the ability to update affective material in WM, diagnosed depressed and never-disordered controls performed an emotion 2-back task in which they were presented with a series of happy, sad, and neutral faces and were asked to indicate whether the current face had the same (match-set) or different (break-set or no-set) emotional expression as that presented two faces earlier. Participants also performed a 0-back task with the same emotional stimuli to serve as a control for perceptual processing. After transforming reaction times to control for baseline group differences, depressed and nondepressed participants exhibited biases in updating emotional content that reflect the tendency to keep negative and positive information active in WM, respectively. Compared with controls, depressed participants were both slower to disengage from sad stimuli and faster to disengage from happy facial expressions. In contrast, nondepressed controls took longer to disengage from happy than from neutral or sad stimuli. These group differences in reaction times may reflect both protective and maladaptive biases in WM that underlie the ability to effectively regulate negative affect.

Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven's Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.

Background

Neurocognitive deficits in fragile X-associated tremor/ataxia syndrome (FXTAS) involve attentional control, working memory, executive functioning, and declarative and procedural learning. To date, no studies comparing FXTAS with other dementias have been done. We characterize the dementia in FXTAS, comparing it with Alzheimer’s disease.

Methods

Retrospective chart review of 68 adults (50 men, 18 women) with FXTAS. 20 men with FXTAS dementia were matched by age, gender, and education to patients with mild Alzheimer's dementia (AD). Neuropsychological measures were compared between the two groups: Boston Naming Test (BNT), phonemic fluency (Controlled Oral Word Association Test), digit span forward (DSF) and backward (DSB). Comparisons were based on analysis of covariance and t-tests to assess significant differences between groups with respect to the neuropsychological measures.

Results

50% of men with FXTAS and no women were cognitively impaired. On mean scores of verbal fluency (22.83 in FXTAS vs. 28.83 in AD, p = 0.112), working memory (DSB, 4.80 in AD vs. 5.41 in FXTAS, p = 0.359), and language (BNT, 48.54 in AD vs. 54.20 in FXTAS, p = 0.089), there were no significant differences. Digit span forward, measuring attention, was significantly higher in subjects with FXTAS dementia (8.59, vs. 7.10 in AD, p = 0.010).

Conclusion

Individuals with FXTAS have significant cognitive deficits, on the order of those in AD although the cognitive profiles in these dementias are not similar. Further research is needed to outline the neuropsychiatric profile in FXTAS and the correlation of genetic markers with the progression and severity of cognitive loss.

The working memory (WM) construct is conceptualized similarly across domains of psychology, yet the methods used to measure WM function vary widely. The present study examined the relationship between WM measures used in the laboratory and those used in applied settings. A large sample of undergraduates completed three laboratory-based WM measures (operation span, listening span, and n-back), as well as the WM subtests from the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale-III. Performance on all of the WM subtests of the clinical batteries shared positive correlations with the lab measures; however, the Arithmetic and Spatial Span subtests shared lower correlations than the other WM tests. Factor analyses revealed that a factor comprising scores from the three lab WM measures and the clinical subtest, Letter-Number Sequencing (LNS), provided the best measurement of WM. Additionally, a latent variable approach was taken using fluid intelligence as a criterion construct to further discriminate between the WM tests. The results revealed that the lab measures, along with the LNS task, were the best predictors of fluid abilities.

A paradigmatic test of executive control, the n-back task, is known to recruit a widely-distributed parietal, frontal and striatal “executive network,” and is thought to require an equally wide array of executive functions. The mapping of functions onto substrates in such a complex task presents a significant challenge to any theoretical framework for executive control. To address this challenge, we developed a biologically-constrained model of the n-back task that emergently develops the ability to appropriately gate, bind, and maintain information in working memory in the course of learning to perform the task. Furthermore, the model is sensitive to proactive interference in ways that match findings from neuroimaging, and shows a U-shaped performance curve after manipulation of prefrontal dopaminergic mechanisms similar to that observed in studies of genetic polymorphisms and pharmacological manipulations. Our model represents a formal computational link between anatomical, functional neuroimaging, genetic, behavioral, and theoretical levels of analysis in the study of executive control. In addition, the model specifies one way in which the prefrontal cortex, basal ganglia, parietal, and sensory cortices may learn to cooperate and give rise to executive control.