Adult age differences in the functional neuroanatomy of verbal recognition memory

Adult age differences are frequently observed in the performance of memory tasks, but the changes in neural function mediating these differences are largely unknown. We used H₂¹⁵O positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) during Encoding, Baseline, and Retrieval conditions of a recognition memory task. Twelve young adults (20–29 years) and 12 older adults (62–79 years) participated. During each task condition, participants made a two‐choice manual response to each of 64 words. Analyses of the performance data yielded evidence of age‐related slowing of encoding and retrieval processes, and an age‐related decline in the accuracy of yes/no recognition (d'). The rCBF activation associated with both encoding and retrieval was greater for older adults than for young adults, but this pattern was more clearly evident for memory retrieval. For young adults, rCBF activation during retrieval occurred primarily in right prefrontal cortex, whereas older adults exhibited a more bilateral pattern of prefrontal activation. Regression analyses predicting reaction time in the memory task from regional PET counts confirmed that the neural system mediating memory retrieval is more widely distributed for older adults than for young adults. Both age groups exhibited some decrease in rCBF activation in the second half of the test session, relative to the first half. The practice‐related decrease in rCBF activation was more prominent for young adults, suggesting that the older adults' recruitment of additional neural systems reflects a more continual allocation of attention to support task performance. Hum. Brain Mapping 7:115–135, 1999. © 1999 Wiley‐Liss, Inc.     

Aging and recognition memory: changes in regional cerebral blood flow associated with components of reaction time distributions.

We used H(2)15O positron emission tomography (PET) to measure age-related changes in regional cerebral blood flow (rCBF) during a verbal recognition memory task. Twelve young adults (20 to 29 years) and 12 older adults (62 to 79 years) participated. Separate PET scans were conducted during Encoding, Baseline, and Retrieval conditions. Each of the conditions involved viewing a series of 64 words and making a two-choice response manually. The complete reaction time (RT) distributions in each task condition were characterized in terms of an ex-Gaussian model (convolution of exponential and Gaussian functions). Parameter estimates were obtained for the mean of the exponential component (tau), representing a task-specific decision process and the mean of the Gaussian component (mu) representing residual sensory coding and response processes. Independently of age group, both tau and mu were higher in the Encoding and Retrieval conditions than in the Baseline condition, and tau was higher during Retrieval than during Encoding. Age-related slowing in task performance was evident primarily in mu. For young adults, rCBF activation in the right prefrontal cortex, in the Retrieval condition, was correlated positively with mu but not with tau. For older adults, rCBF changes (both increases and decreases) in several cortical regions were correlated with both mu and tau. The data suggest that the attentional demands of this task are relatively greater for older adults and consequently lead to the recruitment of additional neural systems during task performance.     

The Myth of Cognitive Decline: Non‐Linear Dynamics of Lifelong Learning

As adults age, their performance on many psychometric tests changes systematically, a finding that is widely taken to reveal that cognitive information‐processing capacities decline across adulthood. Contrary to this, we suggest that older adults' changing performance reflects memory search demands, which escalate as experience grows. A series of simulations show how the performance patterns observed across adulthood emerge naturally in learning models as they acquire knowledge. The simulations correctly identify greater variation in the cognitive performance of older adults, and successfully predict that older adults will show greater sensitivity to fine‐grained differences in the properties of test stimuli than younger adults. Our results indicate that older adults' performance on cognitive tests reflects the predictable consequences of learning on information‐processing, and not cognitive decline. We consider the implications of this for our scientific and cultural understanding of aging.     

Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine

OBJECTIVE: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system. METHOD: In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [15O]H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline. RESULTS: In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration. CONCLUSIONS: Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects.     

Are there gender differences in young vs. aging brains under risk decision-making? <Emphasis Type="Italic">An optical brain imaging study</Emphasis>

Few research publications have reported on gender-dependent neural correlates of risk decision-making in older adults. In this study, we utilized functional near-infrared spectroscopy (fNIRS) to comprehensively investigate both age- and gender-dependent differences in neural correlates in response to a well-utilized risk decision-making protocol, the Balloon Analog Risk Task (BART). A newly-developed technique, atlas-guided diffuse optical tomography (atlas-DOT), was used to image the prefrontal cortices (PFC) of healthy subjects in two age groups (25–40 years; 60–92 years) using BART stimulation. The behavioral measures and brain activations imaged by atlas-DOT were recorded and compared for both age groups. Three-factor analysis of variance was conducted to include all effects of age (young, old), gender (male, female), case (win, lose) and their interactions for both behavioral and hemodynamic responses. The results indicated age differences in cortical activation patterns, activation amplitudes, and brain-behavior correlations. Larger areas of cortical activation with reduced amplitudes in the PFC were observed in older adults when they performed BART. Brain-behavior correlations indicated that young adults took more risks, whereas older adults were more risk-averse. Results also revealed a gender effect in young adults, but not in older adults. Both male and female older adults demonstrated strong PFC responses and the same risk-averse patterns under lose outcomes. This is the first study to examine the neural correlates of risk decisions in older adults by optical brain imaging.     

Neural correlates of memory for object identity and object location: effects of aging

The purpose of this study was to investigate the effects of aging on memory for object identity and object location to determine whether aging affects both posterior neocortical areas that are domain-specific and other brain regions, such as pre-frontal cortex, that are involved in encoding and retrieval regardless of the information that is processed (domain-general). We used positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) in younger and older participants while they were engaged in encoding and retrieving information about object identity and object location. Compared to young adults, older adults showed decreased activation in domain-specific regions of inferior parietal and inferior temporal cortex while engaged in processing (encoding and retrieving) information about object location and object identity, respectively. This decreased specificity in the older adults was accompanied by greater domain-general activation in right prefrontal and premotor cortex during perceptual encoding than during retrieval. Conversely, the younger participants showed greater domain-general activation in right extrastriate cortex (Brodmann area (BA) 18) during retrieval. Moreover, we found that medial temporal and frontal lobes were synergistically activated in younger adults but not in older adults. The pattern of decreased specificity of activation in posterior neocortex with greater activation in anterior neocortex suggests that, with age, compensatory domain-general mechanisms in anterior neocortex are recruited to mitigate altered domain-specific processes. Thus, the results of the present study indicate that the relation between the presumed integrity of various structures, such as the hippocampus, prefrontal cortex, and posterior neocortex, and their pattern of activation, is a complex one that is influenced by age, by the perceptual and cognitive demands of the task and their interaction.     

Prefrontal blood flow dysregulation in drug naive ADHD children without structural abnormalities

Summary. Recent studies suggest a role for prefrontal cortex abnormalities in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). We evaluated young drug-na?ve ADHD outpatients without MRI structural abnormalities to detect prefrontal cortex regional cerebral blood flow (rCBF) functional dysregulation; correlation between age and rCBF; and correlation between symptoms profile and rCBF. Functional brain activities (i.e. rCBF), neuropsychological attention performance and symptom profile were evaluated respectively by single photon emission computerized tomography (SPECT) scan, Stroop Test and the Child Attention Problem Rating Scale. There was a decreased rCBF in the left dorso lateral prefrontal cortex (DLPFC) compared to the right DLPFC of the subjects. In addition, there were positive correlations between age and relative rCBFs of the dorsolateral and orbital prefrontal cortex, and negative correlations between age and absolute rCBFs of the dorsolateral and orbital prefrontal cortex. Finally, higher levels of right relative rCBF and lower levels of left relative rCBF were predictors of higher severity of clinical symptom expression and neuropsychological attention impairment. The results of this study highlight the role of the DLPFC blood flow impairment in the pathogenesis of ADHD even in young subjects without structural abnormalities. Received January 17, 2001; accepted June 12, 2001     

Age-related differences in agenda-driven monitoring of format and task information

Age-related source memory deficits may arise, in part, from changes in the agenda-driven processes that control what features of events are relevant during remembering. Using fMRI, we compared young and older adults on tests assessing source memory for format (picture, word) or encoding task (self-, other-referential), as well as on old–new recognition. Behaviorally, relative to old–new recognition, older adults showed disproportionate and equivalent deficits on both source tests compared to young adults. At encoding, both age groups showed expected activation associated with format in posterior visual processing areas, and with task in medial prefrontal cortex. At test, the groups showed similar selective, agenda-related activity in these representational areas. There were, however, marked age differences in the activity of control regions in lateral and medial prefrontal cortex and lateral parietal cortex. Results of correlation analyses were consistent with the idea that young adults had greater trial-by-trial agenda-driven modulation of activity (i.e., greater selectivity) than did older adults in representational regions. Thus, under selective remembering conditions where older adults showed clear differential regional activity in representational areas depending on type of test, they also showed evidence of disrupted frontal and parietal function and reduced item-by-item modulation of test-appropriate features. This pattern of results is consistent with an age-related deficit in the engagement of selective reflective attention.     

Which obstacle attributes place additional demands on higher-level cognitive function in patients with Parkinson's disease?

BackgroundPrevious reports show that patients with Parkinson's disease (PD) rely on prefrontal activation to compensate for impaired motor function during complex activities such as obstacle negotiation. However, the influence of the properties of the obstacles on prefrontal activation has not been systematically evaluated. Here, we examined the effects of obstacle height and anticipation time on prefrontal activation in patients with PD and older adults.Methods34 patients with PD (age: 67.4 ± 5.7 years; 14 women) and 26 older adults (age: 71.3 ± 8.9 years; 11 women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles (long/short available time response, ART) at heights of 50 mm and 100 mm. Prefrontal activation was measured using functional Near-Infrared Spectroscopy (fNIRS); obstacle negotiation performance was measured using Kinect cameras.ResultsPD patients showed greater increases in prefrontal activation during and after obstacle crossing compared to the older adults (p < 0.001). Obstacle height affected prefrontal activity only when crossing anticipated obstacles (ARTxheight interaction, p = 0.011), in which case higher obstacles were accompanied by higher prefrontal activity. PD patients showed higher levels of activation during unanticipated obstacles, compared to older adults (groupXART: p = 0.015). Different correlations between prefrontal activation and obstacle negotiation strategies were observed in patients and controls.ConclusionsThese results point to the use of prefrontal activation as a compensatory mechanism in PD. Moreover, the higher activation observed when negotiating more challenging obstacles suggests that there is greater reliance on cognitive resources in these demanding situations that may contribute to the higher risk of falls in PD patients.     

Age-related decline of neuroplasticity to intermittent theta burst stimulation of the lateral prefrontal cortex and its relationship with late-life memory performance

ObjectiveAdvanced age is accompanied by a deterioration in memory performance that can profoundly influence activities of daily living. However, the neural processes responsible for age-related memory decline are not fully understood. Here, we used transcranial magnetic stimulation (TMS) in combination with electroencephalography (EEG) to assess age-related changes in neuroplasticity in the human prefrontal cortex.MethodsTMS-evoked cortical potentials (TEPs) were recorded before and following the neuroplasticity-inducing intermittent theta burst stimulation (iTBS), applied to the left lateral prefrontal cortex in healthy young (n = 33, mean age 22 ± 3 years) and older adults (n = 33, mean age 68 ± 7 years).ResultsiTBS increased the amplitude of the positive TEP component at 60 ms after the TMS pulse (P60) in young, but not older adults. This age-related decline in P60 plasticity response was associated with poorer visuospatial associative (but not working) memory performance in older adults.ConclusionsThese findings suggest that neuroplasticity in the human lateral prefrontal cortex is reduced in older relative to young adults, and this may be an important factor in age-related memory decline.SignificanceThis may have important implications for the early detection of cognitive decline and dementia.     

Task-related activity in prefrontal cortex and its relation to recognition memory performance in young and old adults

Older adults often have more widespread prefrontal cortex (PFC) activation during memory retrieval tasks, compared to young adults, particularly in the left hemisphere. Recruitment of additional frontal activity in older adults has been attributed by some researchers to compensation, perhaps for reduced activity elsewhere in the brain, whereas others have described it as a non-selective response that may be due to a failure to inhibit these PFC regions. To address further the impact of PFC activity on memory in older adults, we used PET to measure brain activity during recognition memory tasks. Both young and old adults showed increased activity during recognition, compared to a control task, in bilateral PFC. Young adults showed greater activation of left hippocampus and lateral temporal cortex during recognition, whereas older adults showed greater activity in the right inferior frontal gyrus. Age differences also were seen in correlations between brain activity and memory performance. There were positive correlations between activity in the right parahippocampal gyrus and recognition performance in young adults, whereas positive correlations between activity in PFC and performance were found only in older adults. These positive correlations included the right inferior PFC region where older adults had greater activation. Activity in this right PFC region was negatively correlated with medial temporal activity in both groups. These results provide further evidence for age-specific patterns of brain activity underlying memory performance and are consistent with the idea that PFC assumes a larger role in supporting successful recognition memory with increasing age. The negative correlation between activity in PFC and medial temporal regions, as well as the age differences in how these regions were related to behavior, suggest that those older individuals who recruit PFC to a greater degree may do so as a compensatory response to reductions in medial temporal regions.     

Age-related differences in cortical recruitment and suppression: implications for cognitive performance

The discovery of a coherent set of cortical regions showing activation during rest and deactivation during task performance has reignited an old debate in the field of neuroscience, one that questions the reflexivity of the human brain and provides evidence towards a more intrinsic functional architecture. The default-mode network (DMN) comprising of such consistent cortical regions has become a topic of increasing interest in both healthy and diseased populations. In this study, using a well-examined version of the verbal n-back task, interleaved with periods of rest blocks, we investigated whether the deactivation of the cortical regions comprising the DMN moderates individual differences in behavioral performance in a group of older adults. We recruited 25 young and 25 older adults for our study and presented them with blocks of the n-back task, with varying levels of load, interleaved with periods of fixation. A direct comparison of the young and older participants revealed both a reduction in the up-regulation of the prefrontal and parietal regions in response to increasing task demands, along with a reduction in the down-regulation of DMN regions with increasing cognitive load in the elderly. Better performance in the young adults was associated with the capability to modulate the regions of the working memory network with increasing task difficulty, however enhanced performance in the older cohort was associated with greater load-induced deactivation of the posterior cingulate cortex. This study adds to the existing gamut of aging literature, providing evidence that DMN function is critical to cognitive functioning in older adults.     

Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI

The aim of this study was to investigate whether previously observed hypofrontality in adolescents with attention deficit-hyperactivity disorder (ADHD) during executive functioning [Rubia K, Overmeyer S, Taylor E, Brammer M, Williams S, Simmons A, Andrew C, Bullmore ET. Hypofrontality in attention deficit hyperactivity disorder during higher order motor control: a study using fMRI. Am J Psychiatry 1999;156(6):891-896] could be attributed to delayed maturation of frontal cortex. Brain activation of 17 healthy subjects, 9 adolescents and 8 young adults, during performance of a motor response inhibition task and a motor timing task was measured using functional magnetic resonance imaging (fMRI). The effect of age on brain activation was estimated, using the analysis of variance and regression, at both voxel and regional levels. In the delay task, superior performance in adults was paralleled by a significantly increased power of response in a network comprising prefrontal and parietal cortical regions and putamen. In the stop task, alternative neuronal routes--left hemispheric prefrontal regions in adults and right hemispheric opercular frontal cortex and caudate in adolescents--seem to have been recruited by the two groups for achieving comparable performances. A significant age effect was found for the prefrontal activation in both task, confirming the hypothesis of a dysmaturational pathogenesis for the hypofrontality in ADHD.     

Comparing executive function,evoked hemodynamic response,and gait as predictors of variations in mobility for older adults

Objective: Falls represent a major concern for older adults and may serve as clinically salient index events for those presenting in the prodromal stages of mild cognitive impairment. Declines in executive function performance and in gait consistency have shown promise in predicting fall risk; however, associated neurophysiological underpinnings have received less attention. In this study, we used a multimodal approach to assess fall risk in a group of older adults with and without a previous fall history.

Method: Processing speed, inductive reasoning, verbal fluency, crystallized ability, episodic memory, and executive functioning were assessed using standardized neuropsychological tests. Cognitive interference was assessed using the Multi-Source Interference Task. Spatiotemporal gait parameters were assessed with and without cognitive load using a 6.4-m instrumented walkway. Hemodynamic responses were measured using functional near-infrared spectroscopy.

Results: Whereas no group differences were observed in cognitive behavioral performance, during a cognitive interference task fallers displayed more oxygenated hemoglobin across the prefrontal cortex than nonfallers, suggesting that engaging in the cognitive task was more effortful for them overall, therefore eliciting greater cortical activation. Between-group differences in spatial as well as temporal gait parameters were also observed.

Conclusions: These results are in keeping with assertions that diminished executive control is related to fall risk. Notably, the group differences observed in prefrontal cortical activation and in gait parameters may ultimately precede those observed in cognitive behavioral performance, with implications for measurement sensitivity and early identification.     

Salience and default‐mode network connectivity during threat and safety processing in older adults

The appropriate assessment of threat and safety is important for decision‐making but might be altered in old age due to neurobiological changes. The literature on threat and safety processing in older adults is sparse and it is unclear how healthy ageing affects the brain's functional networks associated with affective processing. We measured skin conductance responses as an indicator of sympathetic arousal and used functional magnetic resonance imaging and independent component analysis to compare young and older adults' functional connectivity in the default mode (DMN) and salience networks (SN) during a threat conditioning and extinction task. While our results provided evidence for differential threat processing in both groups, they also showed that functional connectivity within the SN – but not the DMN – was weaker during threat processing in older compared to young adults. This reduction of within‐network connectivity was accompanied by an age‐related decrease in low frequency spectral power in the SN and a reduction in inter‐network connectivity between the SN and DMN during threat and safety processing. Similarly, we found that skin conductance responses were generally lower in older compared to young adults. Our results are the first to demonstrate age‐related changes in brain activation during aversive conditioning and suggest that the ability to adaptively filter affective information is reduced in older adults.     

Age differences in callosal contributions to cognitive processes

In many cases bilateral cortical activation in older adults has been associated with better task performance, suggesting that a greater reliance on interhemispheric interactions aids performance. Interhemispheric communication is primarily mediated via the corpus callosum (CC), however with advancing age the anterior half of the CC undergoes significant atrophy. Here we determine whether there are age differences in the relationship between cross-sectional area of the CC and performance on cognitive tests of psychomotor processing speed and working memory. We found that older adults had significantly smaller callosal area in the anterior and mid-body of the CC than young adults. Furthermore, older adults with larger size in these callosal areas performed better on assessments of working memory and processing speed. Our results indicate that older adults with larger size of the anterior half of the CC exhibit better cognitive function, although their performance was still poorer than young adults with similar CC size. Thus, while the capability for interhemispheric interactions, as inferred from callosal size, may provide performance benefits for older adults, this capacity alone does not assure protection from general performance decline.     

Age differences in prefontal recruitment during verbal working memory maintenance depend on memory load

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have revealed age-related under-activation, where older adults show less regional brain activation compared to younger adults, as well as age-related over-activation, where older adults show greater activation compared to younger adults. These differences have been found across multiple task domains, including verbal working memory (WM). Curiously, both under-activation and over-activation of dorsolateral prefrontal cortex (DLPFC) have been found for older adults in verbal WM tasks. Here, we use event-related fMRI to test the hypothesis that age-related differences in activation depend on memory load (the number of items that must be maintained). Our predictions about the recruitment of prefrontal executive processes are based on the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH; Reuter-Lorenz and Cappell, 2008). According to this hypothesis, more neural resources are engaged by older brains to accomplish computational goals completed with fewer resources by younger brains. Therefore, seniors are more likely than young adults to show over-activations at lower memory loads, and under-activations at higher memory loads. Consistent with these predictions, in right DLPFC, we observed age-related over-activation with lower memory loads despite equivalent performance accuracy across age groups. In contrast, with the highest memory load, older adults were significantly less accurate and showed less DLPFC activation compared to their younger counterparts. These results are considered in relation to previous reports of activation-performance relations using similar tasks, and are found to support the viability of CRUNCH as an account of age-related compensation and its potential costs.     

ERP amplitude and scalp distribution to target and novel events: effects of temporal order in young,middle-aged and older adults

Event-related brain potentials (ERPs) were recorded from young (mean age = 24.1), middle-aged (48.7) and older (69.7) adults during a version of the oddball paradigm, in which 48 unique, unexpected novel stimuli were interspersed with equally rare instructed targets. As older relative to younger adults are thought to differ in their ability to inhibit the processing of task irrelevant information, we expected, based on previous work, that novel stimuli would retain their ‘novelty’ longer in older than in younger adults. To assess this, P3 amplitude and scalp topography elicited by novels and targets were analyzed as a function of stimulus number (n = 6) within the block and as a function of block number (n = 4). The results were in line with prediction: While the younger adults' P3 scalp distribution shifted from a relatively more frontal to a relatively more posterior focus as a function of novel number within the block, this was not evident in the scalp topographies of the older adults. Coupled with the older adults' elevated false alarm rates to novel stimuli, the data are consistent with a change in frontal lobe function with increases in age.     

Both left and right posterior parietal activations contribute to compensatory processes in normal aging

Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging.     

Is the Alzheimer’s disease cortical thickness signature a biological marker for memory?

Recent work suggests that analysis of the cortical thickness in key brain regions can be used to identify individuals at greatest risk for development of Alzheimer’s disease (AD). It is unclear to what extent this “signature” is a biological marker of normal memory function – the primary cognitive domain affected by AD. We examined the relationship between the AD signature biomarker and memory functioning in a group of neurologically healthy young and older adults. Cortical thickness measurements and neuropsychological evaluations were obtained in 110 adults (age range 21–78, mean?=?46) drawn from the Brain Resource International Database. The cohort was divided into young adult (n?=?64, age 21–50) and older adult (n?=?46, age 51–78) groups. Cortical thickness analysis was performed with FreeSurfer, and the average cortical thickness extracted from the eight regions that comprise the AD signature. Mean AD-signature cortical thickness was positively associated with performance on the delayed free recall trial of a list learning task and this relationship did not differ between younger and older adults. Mean AD-signature cortical thickness was not associated with performance on a test of psychomotor speed, as a control task, in either group. The results suggest that the AD signature cortical thickness is a marker for memory functioning across the adult lifespan.