Zhiwei Zheng

Multimodal intervention in older adults improves resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe

The prefrontal cortex and medial temporal lobe are particularly vulnerable to the effects of aging. The disconnection between them is suggested to be an important cause of cognitive decline in normal aging. Here, using multimodal intervention training, we investigated the functional plasticity in resting-state connectivity of these two regions in older adults. The multimodal intervention, comprised of cognitive training, Tai Chi exercise, and group counseling, was conducted to explore the regional connectivity changes in the default-mode network, as well as changes in prefrontal-based voxel-wise connectivity in the whole brain. Results showed that the intervention selectively affected resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe. Moreover, the strength of resting-state functional connectivity between these regions correlated with individual cognitive performance. Our results suggest that multimodal intervention could postpone the effects of aging and improve the function of the regions that are most heavily influenced by aging, as well as play an important role in preserving the brain and cognition during old age.

Intervention-induced enhancement in intrinsic brain activity in healthy older adults

This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was enhanced for the intervention group, while the control group showed reduced ALFF in these three regions. Moreover, changes in trail-making performance and well-being could be predicted by the intervention-induced changes in ALFF. Additionally, individual differences in the baseline ALFF were correlated with intervention-related changes in behavioral performance. These findings suggest that a multimodal intervention is effective in improving cognitive functions and well-being and can induce functional changes in the aging brain. The study extended previous training studies by suggesting resting-state ALFF as a marker of intervention-induced plasticity in older adults.

Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

The effects of unitization on the contribution of familiarity and recollection processes to associative recognition memory: evidence from event-related potentials.

Familiarity and recollection are two independent cognitive processes involved in recognition memory. It is traditionally believed that both familiarity and recollection can support item recognition, whereas only recollection can support associative recognition. Here, using a standard associative recognition task, we examined whether associative retrieval of unitized associations involved differential patterns of familiarity and recollection processes relative to non-unitized associations. The extent of engagement of familiarity and recollection processes during associative retrieval was estimated by using event-related potentials (ERPs). Twenty participants studied compound words and unrelated word pairs during encoding. Subsequently, they were asked to decide whether a presented word pair was intact, rearranged, or a new pair while electroencephalogram (EEG) was recorded. ERP results showed that compound words evoked a significant early frontal old/new effect (associated with familiarity) between ERPs to intact and rearranged word pairs, whereas this effect disappeared for the unrelated word pairs. In addition, the left parietal old/new effect (associated with recollection) between ERPs to intact and rearranged word pairs was greater for compounds than for unrelated word pairs. These findings suggest that unitization enhances the contribution of both familiarity and recollection processes to associative recognition.

Electrophysiological evidence for the effects of unitization on associative recognition memory in older adults.

Normal aging is associated with greater decline in associative memory relative to item memory due to impaired recollection. Familiarity may also contribute to associative recognition when stimuli are perceived as a unitized representation. Given that familiarity is relatively preserved in older adults, we explored whether age-related associative memory deficits could be attenuated when associations were unitized (i.e., compounds) compared with those non-unitized (i.e., unrelated word pairs). Young and older adults performed an associative recognition task while electroencephalogram (EEG) was recorded. Behavioral results showed that age differences were smaller for recognition of compounds than for unrelated word pairs. ERP results indicated that only compounds evoked an early frontal old/new effect in older adults. Moreover, the early frontal old/new effect was positively correlated with associative discrimination accuracy. These findings suggest that reduced age-related associative deficits under unitized condition may be associated with the presence of familiarity-based retrieval of compounds in older adults.

Unitization improves source memory in older adults: An event-related potential study.

Aging-related decline in episodic memory, particularly in associative memory, is attributed to an impaired recollection of the specific details of a study episode. Fortunately, familiarity is relatively preserved in older adults. Previous studies have indicated that unitization is a specialized form of learning that increases the contribution of familiarity to associative retrieval. Here we examined whether older adults associative memory could be improved when employing an encoding strategy that encouraged unitization. Young and older adults encoded items and background colors either in a unitized condition (i.e., by imagining the color as an internal feature of the item) or in a non-unitized condition (i.e., by imagining the color as a contextual feature of the item). The participants then performed a source recognition test. The effects of unitization on the neural correlates of familiarity were measured by event-related potentials (ERPs). The age differences in source memory performance were lower in the unitized condition than in the non-unitized condition. The older adults only demonstrated neural correlates of familiarity-based source recognition in the unitized condition. These findings suggest that a unitized encoding strategy could improve source memory performance in older adults by enhancing the involvement of familiarity in source recognition.

Neural Correlates of Associative Memory in the Elderly: A Resting-State Functional MRI Study

The neural correlates of associative memory in healthy older adults were investigated by examining the correlation of associative memory performance with spontaneous brain oscillations. Eighty healthy older adults underwent a resting-state functional MRI and took a paired-associative learning test (PALT). Correlations between the amplitude of low-frequency fluctuations (ALFF) as well as fractional ALFF (fALFF) in the whole brain and PALT scores were calculated. We found that spontaneous activity as indexed by both ALFF and fALFF in the parahippocampal gyrus (PHG) was significantly positively correlated with associative memory performance, suggesting that the PHG plays a critical role in associative memory in older people.

Sex Matters: Hippocampal Volume Predicts Individual Differences in Associative Memory in Cognitively Normal Older Women but Not Men

The hippocampus plays a prominent role in associative memory by supporting relational binding and recollection processes. Structural atrophy in the hippocampus is likely to induce associative memory deficits in older adults. Previous studies have primarily focused on average age-related differences in hippocampal structure and memory performance. To date, however, it remains unclear whether individual differences in hippocampal morphometry underlie differential associative memory performance, and whether there are sex differences in the structural correlates of associative memory in healthy older adults. Here, we used voxel-based morphometry (VBM) to examine the extent to which gray matter volume (GMV) of the hippocampus predicts associative memory performance in cognitively normal older adults. Seventy-one participants completed a cued recall paired-associative learning test (PALT), which consists of novel associations and semantically related associations, and underwent magnetic resonance imaging (MRI). We observed worse associative memory performance and larger variability for novel associations than for semantically related associations. The VBM results revealed that higher scores on associative memory for novel associations were related to greater hippocampal GMV across all older adults. When considering men and women separately, the correlation between hippocampal GMV and associative memory performance for novel associations reached significance only in older women. These findings suggest that hippocampal structural volumes may predict individual differences in novel associative memory in older women but not men.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases.

The Default Mode Network Supports Episodic Memory in Cognitively Unimpaired Elderly Individuals: Different Contributions to Immediate Recall and Delayed Recall

While the neural correlates of age-related decline in episodic memory have been the subject of much interest, the spontaneous functional architecture of the brain for various memory processes in elderly adults, such as immediate recall (IR) and delayed recall (DR), remains unclear. The present study thus examined the neural correlates of age-related decline of various memory processes. A total of 66 cognitively normal older adults (aged 60–80 years) participated in this study. Memory processes were measured using the Auditory Verbal Learning Test as well as resting-state brain images, which were analyzed using both regional homogeneity (ReHo) and correlation-based functional connectivity (FC) approaches. We found that both IR and DR were significantly correlated with the ReHo of these critical regions, all within the default mode network (DMN), including the parahippocampal gyrus, posterior cingulate cortex/precuneus, inferior parietal lobule, and medial prefrontal cortex. In addition, DR was also related to the FC between these DMN regions. These results suggest that the DMN plays different roles in memory retrieval across different retention intervals, and connections between the DMN regions contribute to memory consolidation of past events in healthy older people.