Aging gracefully: compensatory brain activity in high-performing older adults

Whereas some older adults show significant cognitive deficits, others perform as well as young adults. We investigated the neural basis of these different aging patterns using positron emission tomography (PET). In PET and functional MRI (fMRI) studies, prefrontal cortex (PFC) activity tends to be less asymmetric in older than in younger adults (Hemispheric Asymmetry Reduction in Old Adults or HAROLD). This change may help counteract age-related neurocognitive decline (compensation hypothesis) or it may reflect an age-related difficulty in recruiting specialized neural mechanisms (dedifferentiation hypothesis). To compare these two hypotheses, we measured PFC activity in younger adults, low-performing older adults, and high-performing older adults during recall and source memory of recently studied words. Compared to recall, source memory was associated with right PFC activations in younger adults. Low-performing older adults recruited similar right PFC regions as young adults, but high-performing older adults engaged PFC regions bilaterally. Thus, consistent with the compensation hypothesis and inconsistent with the dedifferentiation hypothesis, a hemispheric asymmetry reduction was found in high-performing but not in low-performing older adults. The results suggest that low-performing older adults recruited a similar network as young adults but used it inefficiently, whereas high-performing older adults counteracted age-related neural decline through a plastic reorganization of neurocognitive networks.     

Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory

OBJECTIVE: We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. METHODS: We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. RESULTS: compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. CONCLUSIONS: These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM.     

老年人平衡功能的脑网络变化：基于功能性近红外线光谱研究

目的 探究老年人完成平衡控制任务的脑网络特征。方法 2022年1月至4月,于广州医科大学附属第五医院和社区招募22例健康年轻人和20例健康老年人,两组站在足底压力测试板上,完成睁眼或闭眼站立任务,功能性近红外光谱测量左、右前额叶皮质(PFC)和初级运动区(PMC)功能连接强度。结果 老年人闭眼状态下的椭圆面积(Z=-2.884, P <0.01)和最大摆动范围(Z=-2.481, P <0.05)大于年轻人;站立任务时,老年人左侧(t=2.978, P <0.01)和右侧PFC(Z=-3.123, P <0.01)内部功能连接降低;右PMC-左PFC (t=2.087, P <0.05)和右PFC-左PFC (t=3.471, P <0.001)间功能连接降低。结论 与年轻人相比,老年人在平衡控制任务中出现PFC功能连接降低,可能与早期脑老化有关。     

Maintenance versus manipulation in verbal working memory revisited: an fMRI study

Working memory (WM) is the ability to keep a limited amount of information "on line" for immediate use during short intervals. Verbal WM has been hypothesized to consist of neuroanatomically segregated components, i.e., maintenance (storage, rehearsal, and matching) and manipulation (reordering or updating), corresponding to ventrolateral and dorsolateral prefrontal cortex. Previous imaging studies of maintenance vs manipulation processes in WM have produced inconsistent results, which may have been due to methodological issues such as low statistical power and the use of insertion (subtraction) designs. In the present functional magnetic resonance imaging study we used parametric versions of both a prototypical maintenance task (Sternberg) and a prototypical manipulation task (n-letter back task) in 21 healthy subjects. Increased signal correlated with load common for both tasks was found in bilateral dorsolateral and anterior prefrontal, left ventrolateral prefrontal, and bilateral parietal regions. Workload x task interactions were found in bilateral dorsolateral prefrontal cortex for manipulation vs maintenance, but also for responding vs encoding (storage) in the maintenance task. Therefore, our data support a functional rather than a neuroanatomical distinction between maintenance and manipulation, given our finding that these tasks differentially activate virtually identical systems.     

Changing channels: an fMRI study of aging and cross-modal attention shifts

Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an fMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were "shifting" attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition.     

Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks

The prefrontal cortex (PFC) is widely believed to subserve mental manipulation and monitoring processes ascribed to the central executive (CE) of working memory (WM). We attempted to examine and localize the CE by functional imaging of the frontal cortex during tasks designed to require the CE. Using near-infrared spectroscopy, we studied the spatiotemporal dynamics of oxygenated hemoglobin (oxy-Hb), an indicator of changes in regional cerebral blood flow, in both sides of lateral PFC during WM intensive tasks. In most participants, increases in oxy-Hb were localized within one subdivison during performance of the n-back task, whereas oxy-Hb increased more diffusely during the random number generation (RNG) task. Activation of the ventrolateral PFC (VLPFC) was prominent in the n-back task; both sustained and transient dynamics were observed. Transient dynamics means that oxy-Hb first increases but then decreases to less than 50% of the peak value or below the baseline level before the end of the task. For the RNG task sustained activity was also observed in the dorsolateral PFC (DLPFC), especially in the right hemisphere. However, details of patterns of activation varied across participants: subdivisions commonly activated during performance of the two tasks were the bilateral VLPFCs, either side of the VLPFC, and either side of the DLPFC in 4, 2, and 4 of the 12 participants, respectively. The remaining 2 of the 12 participants had no regions commonly activated by these tasks. These results suggest that although the PFC is implicated in the CE, there is no stereotyped anatomical PFC substrate for the CE.     

Support vector machine classification and characterization of age-related reorganization of functional brain networks

Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in negative correlations between the default and sensorimotor networks, are the distinguishing characteristics of age-related reorganization.     

The role of frontopolar cortex in subgoal processing during working memory

Neuroimaging studies have implicated the anterior-most or frontopolar regions of prefrontal cortex (FP-PFC, e.g., Brodmann's Area 10) as playing a central role in higher cognitive functions such as planning, problem solving, reasoning, and episodic memory retrieval. The current functional magnetic resonance imaging (fMRI) study tested the hypothesis that FP-PFC subserves processes related to the monitoring and management of subgoals, while maintaining information in working memory (WM). Subjects were scanned while performing two variants of a simple delayed response WM task. In the control WM condition, subjects monitored for the presence of a specific concrete probe word (LIME) occurring following a specific abstract cue word (FATE). In the subgoal WM condition, subjects monitored for the presence of any concrete probe word immediately following any abstract cue word. Thus, the task required semantic classification of the probe word (the subgoal task), while the cue was simultaneously maintained in WM, so that both pieces of information could be integrated into a target determination. In a second control condition, subjects performed abstract/concrete semantic classification without WM demands. A region within right FP-PFC was identified which showed significant activation during the subgoal WM condition, but no activity in either of the two control conditions. However, this FP-PFC region was not modulated by direct manipulation of active maintenance demands. In contrast, left dorsolateral PFC was affected by active maintenance demands, but the effect did not interact with the presence of a subgoal task. Finally, left ventral PFC regions showed activation in response to semantic classification, but were not affected by WM demands. These results suggest a triple dissociation of function within PFC regions, and further indicate that FP-PFC is selectively engaged by the requirement to monitor and integrate subgoals during WM tasks.     

Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing.

Positron emission tomography was used to investigate common versus specific cortical regions for the maintenance of spatial versus phonological information in working memory (WM). Group and single-subject analyses of regional cerebral blood flow during a new 2 x 2 factorial n-back task were performed. Eight subjects had to memorize either phonological features or the location of serially presented syllables. Brain activation during phonological judgment and spatial judgment (0-back) was compared with that during two corresponding WM conditions (2-back). We observed a common network associated with the requirement of maintaining and sequencing items in WM. Seven or more subjects activated (posterior) superior frontal sulcus (pSFS, BA 6/8, global maximum) and/or adjacent gyri, posterior parietal cortex, and precuneus (BA 7). Less consistently, bilateral middle frontal gyrus (BA 9/46) was involved. Bilateral anterior (BA 39/40) and posterior (BA 7) intraparietal sulcus, as well as right pSFS, exhibited dominance for spatial WM. Although underlying stimulus processing pathways for both types of information were different, no region specific for phonological WM was found. Robust activation within the left inferior frontal gyrus (BA 44 and 45) was present, during both phonological WM and phonological judgment. We conclude that the controversial left prefrontal lateralization for verbal WM reflects more general phonological processing strategies, not necessarily required by tasks using letters. We propose a stimulus-independent role for the bilateral pSFS and its vicinity for maintenance and manipulation of different context-dependent information within working memory.     

Frontal recruitment during response inhibition in older adults replicated with fMRI

Recent research has explored age-related differences in multiple areas of cognitive functioning using fMRI, PET, and SPECT. However, because these studies used different tasks, subjects, and methods, little is known about whether the results of these studies are generalizable or repeatable. The present study replicated a previous study [Psychol. Aging 17 (2002) 56] using the same Go/No-go task with a subset of 11 of the original older adult subjects, and using the same fMRI scanner and imaging methods. A direct comparison was made between these participants at Time 1 and Time 2 for both behavioral and functional data. These participants were also compared to a new young adult group of 11 participants. Although the current young adult group did not perform as well as the original young adult group, the original finding of enhanced left prefrontal activation in older adults relative to younger adults was replicated. Furthermore, when comparing Time 1 to Time 2, older adults exhibited comparable areas of activation, but significantly greater magnitude of activation at Time 1 in a few clusters. The findings indicate that older adults exhibit more bilateral brain activity during this task than young adults, which appears compensatory and is repeatable over time. The magnitude of regional activation, however, may vary with extraneuronal factors such as signal-to-noise ratio or task experience. This study adds to existing research suggesting that bilateral frontal activation is a predominant finding in the aging literature, and not specific to certain tasks in age group comparisons.     

Neuroimaging a single thought: dorsolateral PFC activity associated with refreshing just-activated information.

Neuroimaging studies of human working memory (WM) show conflicting results regarding whether dorsolateral prefrontal cortex (PFC) contributes to maintaining information in consciousness or is recruited primarily when information must be manipulated. Using functional magnetic resonance imaging (fMRI), we looked at a minimal maintenance process--thinking back to a single, just-seen stimulus (refreshing). We found greater activity in left dorsolateral PFC (BA9) when participants refreshed a word compared to reading a word once or a second time. Furthermore, recognition memory was subsequently more accurate and faster for items that had been refreshed, demonstrating that a single thought that maintains activation can have consequences for long-term memory. Our fMRI results call into question any class of models of the functional organization of PFC and WM that associates simple and/or maintenance processes only with ventrolateral PFC or that associates dorsolateral PFC only with more complex processes such as manipulation.     

Developmental changes in category-specific brain responses to numbers and letters in a working memory task

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

Differential effects of age and history of hypertension on regional brain volumes and iron

Aging affects various structural and metabolic properties of the brain. However, associations among various aspects of brain aging are unclear. Moreover, those properties and associations among them may be modified by age-associated increase in vascular risk. In this study, we measured volume of brain regions that vary in their vulnerability to aging and estimated local iron content via T2* relaxometry. In 113 healthy adults (19-83 years old), we examined prefrontal cortex (PFC), primary visual cortex (VC), hippocampus (HC), entorhinal cortex (EC), caudate nucleus (Cd), and putamen (Pt). In some regions (PFC, VC, Cd, and Pt) age-related differences in iron and volume followed similar patterns. However, in the medial-temporal structures, volume and iron content exhibited different age trajectories. Whereas age-related volume reduction was mild in HC and absent in EC, iron content evidenced significant age-related declines. In hypertensive participants significantly greater iron content was noted in all examined regions. Thus, iron content as measured by T2* may be a sensitive index of regional brain aging and may reveal declines that are more prominent than gross anatomical shrinkage.     

Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex

Maintaining relevant information for later use is a critical aspect of working memory (WM). The lateral prefrontal cortex (PFC) and posterior sensory cortical areas appear to be important in supporting maintenance. However, the relative and unique contributions of these areas remain unclear. We have designed a WM paradigm with distraction to probe the contents of maintenance representations in these regions. During delayed recognition trials of faces, selective interference was evident behaviorally with face distraction leading to significantly worse performance than with scene distraction. Event-related fMRI of the human brain showed that maintenance activity in the lateral PFC, but not in visual association cortex (VAC), was selectively disrupted by face distraction. Additionally, the functional connectivity between the lateral PFC and the VAC was perturbed during these trials. We propose a hierarchical and distributed model of active maintenance in which the lateral PFC codes for abstracted mnemonic information, while sensory areas represent specific features of the memoranda. Furthermore, persistent coactivation between the PFC and sensory areas may be a mechanism by which information is actively maintained.     

Complex span tasks and hippocampal recruitment during working memory

The working memory (WM) system is vital to performing everyday functions that require attentive, non-automatic processing of information. However, its interaction with long term memory (LTM) is highly debated. Here, we used fMRI to examine whether a popular complex WM span task, thought to force the displacement of to-be-remembered items in the focus of attention to LTM, recruited medial temporal regions typically associated with LTM functioning to a greater extent and in a different manner than traditional neuroimaging WM tasks during WM encoding and maintenance. fMRI scans were acquired while participants performed the operation span (OSPAN) task and an arithmetic task. Results indicated that performance of both tasks resulted in significant activation in regions typically associated with WM function. More importantly, significant bilateral activation was observed in the hippocampus, suggesting it is recruited during WM encoding and maintenance. Right posterior hippocampus activation was greater during OSPAN than arithmetic. Persitimulus graphs indicate a possible specialization of function for bilateral posterior hippocampus and greater involvement of the left for WM performance. Recall time-course activity within this region hints at LTM involvement during complex span.     

Inter-individual performance differences in younger and older adults differentially relate to amplitude modulations and phase stability of oscillations controlling working memory contents

Efficient encoding of relevant information and suppression of irrelevant information influence working memory (WM) performance, which is limited and declines in adulthood. A cued Sternberg WM task and electroencephalographic recordings (EEG) were used to investigate encoding and control operations in response to to-be-remembered (REM) and not-to-be-remembered (NREM) stimuli in younger and older adults. Younger and older adults selectively remembered REM items in a final recognition memory test. During early stages of stimulus processing, inter-trial phase stability was higher for REM than for NREM items in younger and older adults, presumably reflecting preferential encoding of REM items. At later stages, the oscillatory power of oscillations in the alpha/beta frequency range was higher for NREM than for REM, presumably reflecting the inhibitory top-down suppression of task-irrelevant information. Early phase stability was selectively related to working memory performance in younger adults and high-functioning older adults. The results of this study reveal the differential contributions of low-level feature binding and strategic control components to adult age differences in WM, and show that older adults with more youth-like processing dynamics tend to achieve higher levels of performance.     

Age-Related Changes in Regional Cerebral Blood Flow during Working Memory for Faces

Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood flow (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased. Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal cortex, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time.     

Amplitude modulations and inter-trial phase stability of alpha-oscillations differentially reflect working memory constraints across the lifespan

Working memory (WM) capacity increases across childhood, peaks in young adulthood, and declines thereafter. Developmental and aging theories suggest that deficient inhibitory control processes in children and older adults may underlie the lower performance relative to younger adults. Recently, oscillatory alpha power (7-13 Hz) of the electroencephalogram (EEG) has been suggested as a neural marker of inhibition processes contributing to WM performance (Sauseng et al., 2009). We examined 20 children (10-13 years), 12 younger adults (20-26 years), and 20 older adults (70-76 years) in a cued change-detection paradigm. Behaviorally, we observed the expected lifespan peak in younger adults. EEG alpha power was generally reduced in older adults compared to children and younger adults. In line with previous research, hemispheric differences in alpha power related to attention and WM processes during the retention interval increased with load in younger adults. In children and older adults, lateralized alpha power increased from low to medium load conditions, but decreased for high load conditions. Furthermore, older adults showed higher inter-trial phase stability shortly after stimulus onset compared to children and younger adults. Our results show that inhibitory control processes as indexed by local alpha power modulations can be observed in children and older adults but seem to break down when WM load is high. In addition, older adults are more entrained by external stimulation what may increase a need for inhibitory control during later processing. We conclude that differences in inhibitory control processes and information uptake as reflected in amplitude modulations and inter-trial phase stability of alpha rhythms interactively determine WM constraints across the lifespan.     

Neurophysiology of swallowing: Effects of age and bolus type

This study examined age-related changes in swallowing from an integrated biomechanical and functional imaging perspective in order to more comprehensively characterize changes in swallowing associated with age. We examined swallowing-related fMRI brain activity and videoflouroscopic biomechanics of three bolus types (saliva, water and barium) in 12 young and 11 older adults. We found that age-related neurophysiological changes in swallowing are evident. The group of older adults recruited more cortical regions than young adults, including the pericentral gyri and inferior frontal gyrus pars opercularis and pars triangularis (primarily right-sided). Saliva swallows elicited significantly higher BOLD responses in regions important for swallowing compared to water and barium. In separate videofluoroscopy sessions, we obtained durational measures of supine swallowing. The older cohort had significantly longer delays before the onset of the pharyngeal swallow response and increased residue of ingested material in the pharynx. These findings suggest that older adults without neurological insult elicit more cortical involvement to complete the same swallowing tasks as younger adults.     

Functional significance of age-related differences in motor activation patterns

Recent functional MRI (fMRI) studies have revealed an increased task-related activation in older subjects during a variety of cognitive or perceptual tasks, which may signal beneficial compensatory activity to counteract structural and neurochemical changes associated with aging. Under the assumption that incremental movement rates are associated with an increased functional demand on the motor system, we used fMRI and acoustically paced movements of the right index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to investigate the behavioral significance of additionally recruited brain regions in a group of healthy, older subjects (mean age 66 +/- 8 years) compared with a group of young (mean age 23 +/- 7 years) subjects. The actual tapping frequency (F(1,14) = 0.049, P = 0.829), the tapping interval (F(1,14) = 0.043, P = 0.847), and the error rates (F(1,14) = 0.058, P = 0.743) did not differ significantly between both groups, whereas there was a significant increase in reaction time in the older subjects (F(1,14) = 281.786, P < or = 0.001). At all frequencies, the older subjects demonstrated significant overactivation within the ipsilateral sensorimotor and premotor cortex. However, we did not observe an increased age-related overactivation during higher movements rates in these or other motor regions. Moreover, the magnitude of the hemodynamic response in overactivated regions remained constant across all frequencies. In contrast to cognitive tasks, these findings indicate that an age-related overactivation within the motor system is not related to the functional demand and does not necessarily reflect reorganization to compensate for the neurobiological changes of aging.