A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease

Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68 ± 8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p < .05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78 ± 9% while reaction time averaged 1,027 ± 192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r = 0.61, p = 0.03). There were trends for EF to be related to accuracy (r = 0.47, p = 0.09) and reaction time (r = −0.48, p = 0.09). CO was also related to insula activity (r = 0.60, p = 0.04) and activity in the supplementary motor area activity (r = 0.66, p = 0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.     

Brain region white matter associations with visual selective attention

To understand how normal variations in white matter relate to cognition, magnetization transfer imaging ratios (MTR) of a hypothesized neural network were associated with a test of visual selective attention (VST). Healthy adults (N = 16) without abnormal signal on brain scans viewed a version of DeSchepper and Treisman’s test of VST (1996) with two levels of processing (novel shape matching with and without distractors, contingency feedback). A hypothesized neural network and component regions was significantly associated with accuracy and response times when distractors were present, with betas predicting 55% of variance in accuracy, and 59% of response times. MTR for anterior and posterior cingulate, prefrontal region, and thalami comprised a model predicting 55% of accuracy when distractors were present, and the anterior cingulate accounted for the majority of this effect. Prefrontal MTR predicted longer response times which was associated with increased accuracy. Distal neural areas involved in complex, processing-driven tasks (error processing, response selection, and variable response competition and processing load) may be dependent on white matter fibers to connect distal brain regions/nuclei of a macronetwork, including prefrontal executive functions.     

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention‐deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

The Impact of Age-Related Changes on Working Memory Functional Activity

This work investigated associations of age-related brain atrophy and functional neural networks identified using multivariate analyses of BOLD fMRI data in young and elder participants (young, N = 37; mean age = 25; elders, N = 15; mean age = 74). Two networks were involved in retaining increasing loads of verbal information in working memory. Network utilizations were used to test associations between function and indices of grey matter volume changes using voxel based morphometry. Global changes in brain volume were not associated with the secondary network. Lower regional grey matter volume in the left pre-central gyrus within the primary network was associated with increased secondary network utilization independent of age group. Decreased regional grey matter volume was associated with increased age only in the elders. Increased secondary network expression was associated with increased slope of reaction times across memory load, in the elders. These results support the theory of neural compensation, that elder participants recruit additional neural resources to maintain task performance in the face of age-related decreases in regional grey matter volume.     

The neural correlates of visuo-spatial working memory in children with autism spectrum disorder: effects of cognitive load

Background

Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI).

Methods

We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7–13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load.

Results

Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends.

Conclusions

Children with ASD showed differences in activation in the frontal and parietal lobes—both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.     

Working memory brain activation following severe traumatic brain injury

Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back task that used faces as stimuli. To minimize confusion in TBI patients that was revealed in pilot work, we presented the memory conditions in two separate tasks, 0- versus 1-back and 0- versus 2-back. In the 0- versus 1-back task, OI subjects activated bilateral frontal areas more extensively than TBI patients, and TBI patients activated posterior regions more extensively than OI subjects. In the 0- versus 2-back task, there were no significant differences between the groups. Analysis of changes in activation over time on 1-back disclosed that OI subjects had decreases in bilateral anterior and posterior regions, while TBI patients showed activation increases in those and other areas over time. In the 2-back condition, both groups showed decreases over time in fusiform and parahippocampal gyri, although the OI group also showed increases over time in frontal, parietal, and temporal areas not seen in the TBI patients. The greatest group differences were found in the 1-back condition, which places low demand on WM. Although the extent of activation in the 2-back condition did not differ between the two groups, deactivation in the 2-back condition was seen in the OI patients only, and both groups' patterns of activation over time varied, suggesting a dissociation between the TBI and OI patients in recruitment of neural areas mediating WM.     

Failing Compensatory Mechanisms During Working Memory in Older Apolipoprotein E-ε4 Healthy Adults

How and when the known genetic risk allele, apolipoprotein E-ε4 (APOEε4), confers risk to Alzheimer’s disease has yet to be determined. We studied older adults and found that APOEε4 carriers had greater neural activation in the medial frontal and parahippocampal gyrus during a memory task (cluster-corrected p < .01). When compared to a group of younger adults, interactive effects of age and APOEε4 were found in the inferior frontal—anterior temporal region, one of the first areas to develop amyloid plaques in patients with Alzheimer’s disease, and, in the posterior cingulate, one of the earliest areas to show decreased cerebral metabolism in Alzheimer’s disease. Thus, abnormally high activation in fronto-temporal areas are present in both younger and older APOEε4 carriers confronted with a working memory task when compared to non-APOEε4 carriers. This effect, however, appears to diminish with age.     

Functional connectivity measured with magnetoencephalography identifies persons with HIV disease

There is need for a valid and reliable biomarker for HIV Associated Neurocognitive Disorder (HAND). The purpose of the present study was to provide preliminary evidence of the potential utility of neuronal functional connectivity measures obtained using magnetoencephalography (MEG) to identify HIV-associated changes in brain function. Resting state, eyes closed, MEG data from 10 HIV-infected individuals and 8 seronegative controls were analyzed using mutual information (MI) between all pairs of MEG sensors to determine whether there were functional brain networks that distinguished between subject groups based on cognition (global and learning) or on serostatus. Three networks were identified across all subjects, but after permutation testing (at α < .005) only the one related to HIV serostatus was significant. The network included MEG sensors (planar gradiometers) above the right anterior region connecting to sensors above the left posterior region. A mean MI value was calculated across all connections from the anterior to the posterior groupings; that score distinguished between the serostatus groups with only one error (sensitivity = 1.00, specificity = .88 (X ²  = 15.4, df = 1, p < .01, Relative Risk = .11). There were no significant associations between the MI value and the neuropsychological Global Impairment Rating, substance abuse, mood disorder, age, education, CD4+ cell counts or HIV viral load. We conclude that using a measure of functional connectivity, it may be possible to distinguish between HIV-infected and uninfected individuals, suggesting that MEG may have the potential to serve as a sensitive, non-invasive biomarker for HAND.     

Parametric manipulation of working memory load in traumatic brain injury: behavioral and neural correlates.

Traumatic brain injury (TBI) is often associated with enduring impairments in high-level cognitive functioning, including working memory (WM). We examined WM function in predominantly chronic patients with mild, moderate and severe TBI and healthy comparison subjects behaviorally and, in a small subset of moderate-to-severe TBI patients, with event-related functional magnetic resonance imaging (fMRI), using a visual n-back task that parametrically varied WM load. TBI patients showed severity-dependent and load-related WM deficits in performance accuracy, but not reaction time. Performance of mild TBI patients did not differ from controls; patients with moderate and severe TBI were impaired, relative to controls and mild TBI patients, but only at higher WM-load levels. fMRI results show that TBI patients exhibit altered patterns of activation in a number of WM-related brain regions, including the dorsolateral prefrontal cortex and Broca's area. Examination of the pattern of behavioral responding and the temporal course of activations suggests that WM deficits in moderate-to-severe TBI are due to associative or strategic aspects of WM, and not impairments in active maintenance of stimulus representations. Overall, results demonstrate that individuals with moderate-to-severe TBI exhibit WM deficits that are associated with dysfunction within a distributed network of brain regions that support verbally mediated WM.     

Dopaminergic challenge with bromocriptine one month after mild traumatic brain injury: altered working memory and BOLD response

Catecholamines, particularly dopamine, modulate working memory (WM). Altered sensitivity to dopamine might play a role in WM changes observed after traumatic brain injury (TBI). Thirty-one healthy controls (HC) and 26 individuals with mild TBI (MTBI) 1 month after injury were challenged with bromocriptine versus placebo before administration of a verbal WM functional MRI task. Bromocriptine was associated with improved WM performance in the HC but not the MTBI group. On bromocriptine, the MTBI group showed increased activation outside of a task-specific region of interest. Findings are consistent with the hypothesis that individuals with MTBI have altered responsivity to dopamine.     

Brain-behavior relationships in young traumatic brain injury patients: Fractional anisotropy measures are highly correlated with dynamic visuomotor tracking performance

Traumatic brain injury (TBI) patients have a high incidence of eye-hand coordination deficits. Diffuse axonal injury is common in TBI and is presumed to contribute to persistent motor problems. Using Diffusion Tensor Imaging (DTI), this study sought to identify changes in (sensori)motor white matter (WM) pathways/regions in a TBI group during the chronic recovery stage. A secondary objective was to examine the relationship between WM integrity and upper-limb visuomotor tracking performance. A young TBI (n = 17) and control (n = 14) group performed a dynamic tracking task, characterized by increasing information processing speed and predictive movement control. DTI scans were administered along with standard anatomical scans. The TBI group was found to perform inferior to the control group on the tracking task. Decreased fractional anisotropy was found in the TBI group in dedicated pathways involved in transmission of afferent and efferent information, i.e., corticospinal tract, posterior thalamic radiation, and optic radiation, due to increased diffusivity parallel and perpendicular to axonal fibre direction. This decrease in WM integrity was associated with inferior visuomotor tracking performance. Moreover, discriminant function analysis demonstrated that the model, based on the combined application of DTI and behavioral measures, was the most effective in distinguishing between TBI patients and controls. This study shows that specific eye-hand coordination deficits in a young TBI group are related to microstructural abnormalities in task-specific cerebral WM structures. Measures of white matter integrity are potentially important biomarkers for TBI that may support prognosis of motor deficits.     

Correlations between EEG and clinical outcome in chronic neuropathic pain: surgical effects and treatment resistance

Chronic neuropathic pain may require a neurosurgical treatment, but for reasons that have not been fully explored yet, a significant number of patients do not benefit from the intervention. We compared the resting EEG of 15 healthy controls to the EEG of 23 chronic neuropathic pain patients before and 12 months after treatment by the central lateral thalamotomy (CLT). A patient subgroup had a high (n = 14, pain relief (PR) ≥ 50%) and another subgroup a low (n = 9, PR < 50%) postoperative PR. EEG spectral power and source localization of the high PR patients were normalized postoperatively. In contrast, low PR patients showed postoperative maintenance of insular, cingulate and prefrontal overactivities, and their frustration values were positively correlated with cingulate and prefrontal activity. These findings demonstrate a normalizing effect of CLT on cortical activity and suggest that treatment resistance is associated with a frustration-based dynamics.     

Atorvastatin Therapy is Associated with Greater and Faster Cerebral Hemodynamic Response

Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer’s disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imaging of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n = 8) and placebo (n = 7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.     

Antipyretic treatment of noninfectious fever in children with severe traumatic brain injury

Objective The purpose of this study was to describe the treatment of noninfectious fever in children with severe traumatic brain injury (TBI). Materials and methods We conducted a retrospective study to compare type of and response to antipyretic treatment strategies in children less than or equal to 17 years and Glasgow Coma Scale (GCS) score less than 9. Results The average admission GCS score was 4. Forty children (35 boys, 5 girls), age 7.8 ± 5.2 years, had noninfectious fever. Seventy percent (28 of 40) received acetaminophen only, and 30% (12 of 40) received acetaminophen plus either ibuprofen or physical cooling. Time to next febrile episode was longer in patients receiving combination therapy than those receiving monotherapy (p = 0.03). Fever refractory to treatment dose or strategy occurred in more than 40% of the patients. Conclusions Early combination antipyretic therapy may be needed to effectively maintain normothermia in children with severe TBI.     

Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury

Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained “resting state” in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.     

The neurodevelopmental differences of increasing verbal working memory demand in children and adults

Working memory (WM) – temporary storage and manipulation of information in the mind – is a key component of cognitive maturation, and structural brain changes throughout development are associated with refinements in WM. Recent functional neuroimaging studies have shown that there is greater activation in prefrontal and parietal brain regions with increasing age, with adults showing more refined, localized patterns of activations. However, few studies have investigated the neural basis of verbal WM development, as the majority of reports examine visuo-spatial WM.We used fMRI and a 1-back verbal WM task with six levels of difficulty to examine the neurodevelopmental changes in WM function in 40 participants, twenty-four children (ages 9–15 yr) and sixteen young adults (ages 20–25 yr). Children and adults both demonstrated an opposing system of cognitive processes with increasing cognitive demand, where areas related to WM (frontal and parietal regions) increased in activity, and areas associated with the default mode network decreased in activity. Although there were many similarities in the neural activation patterns associated with increasing verbal WM capacity in children and adults, significant changes in the fMRI responses were seen with age. Adults showed greater load-dependent changes than children in WM in the bilateral superior parietal gyri, inferior frontal and left middle frontal gyri and right cerebellum. Compared to children, adults also showed greater decreasing activation across WM load in the bilateral anterior cingulate, anterior medial prefrontal gyrus, right superior lateral temporal gyrus and left posterior cingulate. These results demonstrate that while children and adults activate similar neural networks in response to verbal WM tasks, the extent to which they rely on these areas in response to increasing cognitive load evolves between childhood and adulthood.     

Aberrant anterior cingulate activation in obsessive-compulsive disorder is related to task complexity

ObjectivesEvidence for working memory (WM) deficits in obsessive–compulsive disorder (OCD) is increasing. However, findings regarding the underlying neural substrates are heterogeneous. Moreover, the influence of cognitive demand on the severity of these deficits and associated activation alterations is a matter of debate.MethodsTo further address this question the present fMRI study examined a sample of 21 predominantly medication-free inpatients with OCD and 21 matched healthy volunteers using a parametric verbal n-back task.ResultsIn agreement with earlier studies patients exhibited focused activation alterations that could be found to be critically dependent on WM demands: There were no differences in activation between patients and healthy volunteers under low cognitive demands. However, patients exhibited a significantly decreased activation in the dorsal anterior cingulate cortex (dACC) in association with increasing task demands. While dACC activation in controls showed a linear increase with increasing task demands, this linearity was not detectable in patients with OCD.ConclusionsPresent findings provide further support for the relevance of the anterior cingulate in OCD and illustrate that both task demands and task processes are of major influence in this context.     

Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial

The objective of this study was to test whether a previous observed Acetyl-L-carnitine (ALC) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This was a six-week, randomized clinical trial undertaken in an outpatient child and adolescent clinic. Subjects included 40 outpatients (28 boys and 12 girls) between the ages of 7–13 who met the DSM-IV-TR diagnostic criteria for ADHD. All study subjects were randomly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylphenidate at a dose of 20–30 mg/day depending on weight or Placebo plus methylphenidate at a dose of 20–30 mg/day depending on weight. The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV. No difference was observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.10; P = 0.74 and df = 1; F = 0.22; P = 0.63 respectively). Side effects consisting of headache and irritability were observed more frequently in the methylphenidate plus placebo group. The results of this study do not support the application of ALC as an adjunctive therapy to methylphenidate in children and adolescents with ADHD.     

Neural correlates of self-evaluative accuracy after traumatic brain injury

Individuals who have sustained a traumatic brain injury (TBI) often exhibit an array of cognitive deficits, yet perhaps most maladaptive of these sequelae is the frequent occurrence of reduced insight into one's own condition. In such cases, TBI individuals may overestimate their post-injury level of socio-cognitive functioning, leading to disparities between how they perceive themselves and what others observe. This functional MRI (fMRI) investigation examined the relationship between level of insight into one's post-injury condition (i.e. trait/ability status) and neural activation evoked during an fMRI task involving self-appraisal of one's traits and abilities. Twenty TBI patients (8-12 weeks post-injury, ER Glasgow Coma Scale Average = 10.9+/-2.8) were selected on the criterion that they overestimate their current trait/abilities (as detected on the patient competency rating scale, PCRS). fMRI activation on the self-appraisal task was compared between the TBI patients and 20 matched controls. For both groups, the fMRI task evoked activation at mid-line prefrontal and retrosplenial cortices. TBI patients exhibited greater signal change in the anterior cingulate, precuneus and right temporal pole. Subsequently, a linear regression analysis was conducted for the TBI group, with the PCRS and a measure of cognitive speed entered as predictor variables to determine the selective effect of insight on self-evaluative brain activation. A more accurate level of trait/ability-based insight was related to increased signal change in the right anterior dorsal prefrontal cortex (PFC). The results suggest that one's post-injury level of self-referential insight is related to a network inclusive of the medial and right dorsal PFC.     

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive–negative working memory (PN_wm) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN_wm component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN_wm area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.