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Biomedical subjects

Adriaan A Lammertsma

Publications and source records attributed to Adriaan A Lammertsma.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.

The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.

Aged↗
PubMed2006

Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators.

OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using positron emission tomography (PET), during chronic and acute sacral neuromodulation (SN). SN is an effective long-term treatment for chronic urge incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and supraspinal structures are probably responsible for the action of SN. It is not known which brain areas are involved, and the optimum benefit of SN is not immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS AND METHODS: Brain activity was measured in two groups: 12 urge incontinent patients (11 women and one man; mean age 52 years) in whom an implanted unilateral S3 nerve neurostimulator had been effective for >6 months (mean time after implantation 4.5 years); and eight urge incontinent patients (seven women and one man; mean age 49 years) in whom the neurostimulator was activated for the first time in the PET scanner. RESULTS: During SN in chronically implanted patients, there were significant decreases in rCBF in the middle part of the cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex. During acute SN in newly implanted patients, there were significant decreases in rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex, the right insular cortex and the ventromedial orbitofrontal cortex. Group analysis between chronic and newly implanted patients showed significant differences in the associative sensory cortex, premotor cortex and the cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings suggests that chronic SN influences, presumably via the spinal cord, brain areas previously implicated in detrusor hyperactivity, awareness of bladder filling, the urge to void and the timing of micturition. Furthermore, SN affects areas involved in alertness and awareness. Acute SN modulates predominantly areas involved in sensorimotor learning, which might become less active during the course of chronic SN.

Acute Disease↗
PubMed2006

FDG PET as a predictor of response to resynchronisation therapy in patients with ischaemic cardiomyopathy.

PURPOSE: Although resynchronisation therapy (CRT) is a promising addition to heart failure therapy, a substantial number of patients do not respond to CRT. As FDG PET has routinely been used for prediction of improvement after revascularisation in ischaemic cardiomyopathy, it was hypothesised that there is also a relationship between the extent of viable tissue and improvement as a result of CRT. METHODS: Thirty-nine patients with ischaemic cardiomyopathy (ejection fraction 27 +/- 9%) and a wide QRS complex underwent temporary pacing to determine the optimal pacing combination, i.e. that with the highest increase in cardiac index (CI) compared with baseline (measured by Doppler echocardiography). All patients also underwent FDG PET imaging. In 19 patients, CI measurements were repeated 10-12 weeks after permanent biventricular pacemaker implantation. RESULTS: Echocardiography (13-segment model) showed a mean of 9.8 +/- 1.6 dyssynergic segments, with preserved FDG uptake in 4.1 +/- 2.4 segments. CI improvement at the optimal pacing site was 20 +/- 9%. There was a linear relationship between the extent of viable tissue and CI improvement during pacing (p < 0.001). Using a cut-off value of more than three viable segments (ROC analysis), FDG PET had a sensitivity of 72% and a specificity of 71% for detection of the presence of haemodynamic improvement (i.e. a CI improvement >15%). The relation between CI improvement and viable tissue was similar at follow-up. CONCLUSION: A correlation was found between the extent of viable tissue and the haemodynamic response to CRT in patients with ischaemic cardiomyopathy, suggesting that FDG PET imaging may be useful to discriminate between responders and non-responders to CRT.

Aged↗
PubMed2006

Optimization algorithms and weighting factors for analysis of dynamic PET studies.

Positron emission tomography (PET) pharmacokinetic analysis involves fitting of measured PET data to a PET pharmacokinetic model. The fitted parameters may, however, suffer from bias or be unrealistic, especially in the case of noisy data. There are many optimization algorithms, each having different characteristics. The purpose of the present study was to evaluate (1) the performance of different optimization algorithms and (2) the effects of using incorrect weighting factors during optimization in terms of both accuracy and reproducibility of fitted PET pharmacokinetic parameters. In this study, the performance of commonly used optimization algorithms (i.e. interior-reflective Newton methods) and a simulated annealing (SA) method was evaluated. This SA algorithm, known as basin hopping, was modified for the present application. In addition, optimization was performed using various weighting factors. Algorithms and effects of using incorrect weighting factors were studied using both simulated and clinical time-activity curves (TACs). Input data, taken from [(15)O]H(2)O, [(11)C]flumazenil and [(11)C](R)-PK11195 studies, were used to simulate time-activity curves at various variance levels (0-15% COV). Clinical evaluation was based on studies with the same three tracers. SA was able to produce accurate results without the need for selecting appropriate starting values for (kinetic) parameters, in contrast to the interior-reflective Newton method. The latter gave biased results unless it was modified to allow for a range of starting values for the different parameters. For patient studies, where large variability is expected, both SA and the extended Newton method provided accurate results. Simulations and clinical assessment showed similar results for the evaluation of different weighting models in that small to intermediate mismatches between data variance and weighting factors did not significantly affect the outcome of the fits. Large errors were observed only when the mismatch between weighting model and data variance was large. It is concluded that selection of specific optimization algorithms and weighting factors can have a large effect on the accuracy and precision of PET pharmacokinetic analysis. Apart from carefully selecting appropriate algorithms and variance models, further improvement in accuracy might be obtained by using noise reducing strategies, such as wavelet filtering, provided that these methods do not introduce significant bias.

Algorithms↗
PubMed2006

Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[11C]verapamil and PET.

Diminished P-glycoprotein (P-gp)-mediated transport across the blood-brain barrier may play an important role in several neurodegenerative disorders. In previous studies, a racemic mixture of (R)-[(11)C]verapamil and (S)-[(11)C]verapamil has been used as tracer for assessing P-gp function using positron emission tomography (PET). Quantification, however, is compromised by potential differences in kinetics between these two isomers. The aim of the present study was to evaluate the kinetics of pure (R)-[(11)C]verapamil in humans and to develop a tracer kinetic model for the analysis of P-gp-mediated transport of (R)-[(11)C]verapamil, including the putative contribution of its radioactive metabolites. Dynamic (R)-[(11)C]verapamil PET scans of 10 male volunteers were analysed with various single- or two-tissue compartment models, with separate compartments for N-dealkylated and N-demethylated metabolites, assuming that either (R)-[(11)C]verapamil alone or (R)-[(11)C]verapamil and any combination of metabolites cross the BBB. In addition, six of the subjects underwent two (R)-[(11)C]verapamil scans to evaluate test-retest reliability. One hour after injection, 50% of total plasma radioactivity consisted of labelled metabolites. Most models fitted the data well and the analysis did not point to a definite 'best' model, with differences in optimal model between subjects. The lowest mean test-retest variability (2.9%) was found for a single-tissue model without any metabolite correction. Models with separate metabolite compartments lead to high test-retest variability. Assuming that differences in kinetics of (R)-[(11)C]verapamil and N-dealkylated metabolites are small, a one input, one-tissue model with correction for N-demethylated metabolites only leads to a good compromise between fit quality and test-retest variability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.

PURPOSE: Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. EXPERIMENTAL DESIGN: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq (89)Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. RESULTS: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. CONCLUSION: In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Aged↗
PubMed2006

Evaluation of reference tissue models for the analysis of [11C](R)-PK11195 studies.

[(11)C](R)-PK11195 is a marker of activated microglia, which can be used to measure inflammation in neurologic disorders. The purpose of the present study was to define the optimal reference tissue model based on a comparison with a validated plasma input model and using clinical studies and Monte Carlo simulations. Accuracy and reproducibility of reference tissue models were evaluated using Monte Carlo simulations. The effects of noise and variation in specific binding, nonspecific binding and blood volume were evaluated. Dynamic positron emission tomography scans were performed on 13 subjects, and radioactivity in arterial blood was monitored online. In addition, blood samples were taken to generate a metabolite corrected plasma input function. Both a (validated) two-tissue reversible compartment model with K(1)/k(2) fixed to whole cortex and various reference tissue models were fitted to the data. Finally, a simplified reference tissue model (SRTM) corrected for nonspecific binding using plasma input data (SRTM(pl_corr)) was investigated. Correlations between reference tissue models (including SRTM(pl_corr)) and the plasma input model were calculated. Monte Carlo simulations indicated that low-specific binding results in decreased accuracy and reproducibility. In this respect, the SRTM and SRTM(pl_corr) performed relatively well. Varying blood volume had no effect on performance. In the clinical evaluation, SRTM(pl_corr) and SRTM had the highest correlations with the plasma input model (R(2)=0.82 and 0.78, respectively). SRTM(pl_corr) is optimal when an arterial plasma input curve is available. Simplified reference tissue model is the best alternative when no plasma input is available.

Adult↗
PubMed2006

How should we analyse FDG PET studies for monitoring tumour response?

FDG PET is a promising technique for monitoring tumour response early during anticancer therapy. Progress, however, has been limited owing to the multitude of methods currently in use. Here, the most promising techniques for multi-centre trials are discussed briefly, with emphasis on the need for standardisation. In addition, an approach is presented for response monitoring studies using newly developed drugs. This approach makes use of a large database of response monitoring studies, which defines the relationship between simplified clinical methods and full quantitative analysis for classic cytotoxic drugs. For a new drug, first a pilot study is performed to assess whether it affects this relationship. Based on this pilot, it is decided whether or not a simplified clinical method can be used in further studies.

Fluorodeoxyglucose F18↗
PubMed2006

Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography.

INTRODUCTION: P-glycoprotein (P-gp) is an efflux transporter responsible for the transport of various drugs across the blood-brain barrier (BBB). Loss of P-gp function with age may be one factor in the development and progression of neurodegenerative diseases. The aim of this study was to assess the effect of aging on BBB P-gp function. Furthermore, the relationship between BBB P-gp activity and peripheral P-gp activity in CD3-positive leukocytes was investigated. Finally, plasma pharmacokinetics of carbon 11-labeled (R)-verapamil was evaluated. METHODS: (R)-[(11)C]verapamil and positron emission tomography were used to assess gray matter P-gp function. Because (R)-[(11)C]verapamil is a substrate for P-gp, the volume of distribution of (R)-[(11)C]verapamil in the brain inversely reflects P-gp function in the BBB. RESULTS: Mean volume of distribution values for 5 young healthy volunteers (age range, 21-27 years) and 5 elderly healthy volunteers (age range, 59-68 years) were 0.62+/-0.10 and 0.73+/-0.07, respectively (P=.03). The activity index of P-gp activity in CD3-positive leukocytes was 2.88+/-0.77 in young volunteers and 1.76+/-0.58 in elderly volunteers (P=.02). CONCLUSION: This study showed decreased P-gp activity during aging. Consequently, the brain may be exposed to higher drug and toxin levels in elderly subjects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Quantification of myocardial perfusion using intravenous myocardial contrast echocardiography in healthy volunteers: comparison with positron emission tomography.

BACKGROUND: Intravenous myocardial contrast echocardiography (ivMCE) has the potential to evaluate myocardial contraction and perfusion simultaneously. The purpose of this study was to assess quantification of myocardial blood flow (MBF) using ivMCE and to compare this with MBF as measured with positron emission tomography (PET). METHODS: A total of 16 healthy volunteers underwent ivMCE using power pulse inversion and contrast agent microbubbles at rest and during pharmacologically induced vasodilation. Microbubble destruction was achieved with a burst of high-energy ultrasound, followed by imaging of contrast replenishment with low-energy ultrasound. Regions of interest were drawn and time intensity curves were calculated that were fitted to a monoexponential function. An estimate of MBF (perfusion estime) was calculated as the product of the plateau value A and the exponential beta describing the replenishment curve. MBF was measured with PET using oxygen-15-labeled water at rest and during adenosine stress. RESULTS: Significant correlations were found between MBF as measured with PET and perfusion estimate as measured with ivMCE in the left anterior descending coronary artery (r = 0.87, P < .01), right coronary artery (r = 0.66, P < .01), and left circumflex artery (r = 0.75, P < .01) territories. Heterogeneity, however, was significantly larger for ivMCE (coefficient of variation 32 +/- 15%) than for PET (9 +/- 6%) measurements (P < .01). CONCLUSION: Perfusion parameters as measured with ivMCE correlated with PET-derived MBF, but associated heterogeneity was significantly larger. Currently, this heterogeneity precludes true quantification of MBF using ivMCE.

Adult↗
PubMed2006

Regional heterogeneity of resting perfusion in hypertrophic cardiomyopathy is related to delayed contrast enhancement but not to systolic function: a PET and MRI study.

BACKGROUND: Regional differences in resting myocardial blood flow (MBF) have been observed in patients with hypertrophic cardiomyopathy (HCM), but their determinants are currently unknown. This study verifies whether MBF at rest in HCM is related to delayed contrast enhancement (DCE) or regional systolic function (or both) as determined by magnetic resonance imaging. METHODS AND RESULTS: Fourteen patients with HCM were studied. MBF was measured with positron emission tomography by use of oxygen 15-labeled water. DCE and tissue tagging, to calculate end-systolic circumferential shortening (Ecc), were obtained with magnetic resonance imaging. The mean resting MBF was 0.78 +/- 0.19 mL x min(-1) x mL(-1), and there was a trend toward reduced MBF in the septum (0.72 +/- 0.11 mL x min(-1) x mL(-1)) compared with that in the lateral wall (0.84 +/- 0.29 mL x min(-1) x mL(-1)) (P = .092). The distribution patterns of DCE and Ecc were both heterogeneous, displaying significantly increased enhancement and impaired regional systolic function in the hypertrophic septum compared with the lateral wall (both P < .001). Resting MBF was inversely related to the extent of DCE (r = -0.30, P < .001), whereas MBF was not significantly related to Ecc (r = -0.15, P = .072). CONCLUSIONS: Regional heterogeneity of resting perfusion in HCM is related to the extent of DCE but not to regional systolic function.

Adult↗
PubMed2006

Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand.

The potent histamine H(3) receptor antagonist JNJ-10181457 (1) was successfully labeled with (11)C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28+/-8%) and high specific radioactivity (56+/-26 GBq/mumol). The binding of [(11)C]1 to H(3) receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [(11)C]1 in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H(3) antagonists, JNJ-5207852 (2) and unlabeled Compound (1), in a concentration-dependent manner. The biodistribution of [(11)C]1 in rats was measured at 5, 10, 30 and 60 min. The uptake of [(11)C]1 in regions rich in H(3) receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [(11)C]1 in the rat brain could not be blocked by pretreatment with either Compound (2) (30 min or 24 h pretreatment) or cold Compound (1) (30-min pretreatment). The biodistribution of [(11)C]1 in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H(3)(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [(11)C]1 could not specifically label H(3) receptors in rodent brain in vivo. Possible causes are discussed.

Animals↗
PubMed2006

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study.

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.

Adult↗
PubMed2005

Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer.

PURPOSE: The objective of this study was to determine the accuracy of (early) response measurements using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) with respect to survival of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) undergoing induction chemotherapy (IC), with a comparative analysis of PET methods. PATIENTS AND METHODS: In a prospective multicenter study, PET was performed in patients before IC and after one and three cycles. Computed tomography (CT) was performed before and after IC. Glucose consumption (metabolic rate of glucose [MRglu]) was measured using Patlak graphical analysis and correlated with simplified methods. Mediastinal lymph node (MLN) status was assessed visually. Cox proportional hazards analysis was used to determine the prognostic relevance of CT and PET measures of response with respect to survival. RESULTS: Complete PET data sets were available in 47 patients. Median survival was 21 months. MLN status after IC by PET predicted survival (hazard ratio [HR], 2.33; 95% CI, 1.04 to 5.22; P = .04) in contrast with CT (HR, 1.87; 95% CI, 0.81 to 4.30; P = .14). Residual MRglu after IC proved to be the best prognostic factor (HR, 1.95; 95% CI, 1.28 to 2.97; P = .002). Multivariate stepwise analysis showed that PET identified prognostically different strata in patients considered responsive according to CT. Residual MRglu after one cycle selected patients with different outcomes (HR, 2.04; 95% CI, 1.18 to 3.52; P = .01). Simplified quantitative 18FDG PET methods were correlated with Patlak graphical analysis during and after therapy (r > or = 0.90). CONCLUSION: 18FDG PET has additional value over CT in monitoring response to IC in patients with stage IIIA-N2 NSCLC, and it seems feasible to predict survival early during IC. Simple semiquantitative and complex PET methods perform equally well.

Adult↗
PubMed2005

Memory performance and the growth hormone/insulin-like growth factor axis in elderly: a positron emission tomography study.

The relationship between the growth hormone/insulin-like growth factor (GH-IGF)-I status and memory performance is studied in 24 elderly males and females, aged 75-85 years. Positron emission tomography (PET) was used to measure differences in regional cerebral blood flow during the performance of a delayed-non-match-to-sample (DNMTS) working memory task. Quality and speed of performance on the DNMTS task were measured separately for the easy items (3, 4 and 5 letters) and difficult items (6, 7 and 8 letters). Results were analyzed in two different groups based on the IGF-I level of the subjects (low or high IGF-I). Error rates on the working memory task were not different, but the high IGF-I group had shorter reaction times on the easy items. The high IGF-I group showed a significantly greater increase in cerebral blood flow in the left premotor cortex (easy items) and left dorsolateral prefrontal cortex (difficult items) compared to the low IGF-I group. It is concluded that elderly with high IGF-I levels are capable of faster working memory performance and increased recruitment of task-associated prefrontal regions.

Aged↗